Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and ...Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.展开更多
Hepatocellular carcinoma(HCC)remains one of the most prevalent and lethal malignancies worldwide.Long non-coding RNAs(lncRNAs)have emerged as crucial regulators of gene expression and cancer progression,yet the functi...Hepatocellular carcinoma(HCC)remains one of the most prevalent and lethal malignancies worldwide.Long non-coding RNAs(lncRNAs)have emerged as crucial regulators of gene expression and cancer progression,yet the functional diversity of RP11-derived lncRNAs—originally mapped to bacterial artificial chromosome(BAC)clones from the Roswell Park Cancer Institute—has only recently begun to be appreciated.This mini-review aims to systematically synthesize current findings on RP11-derived lncRNAs in HCC,outlining their genomic origins,molecular mechanisms,and biological significance.We highlight their roles in metabolic reprogramming,microRNA network modulation,and tumor progression,as well as their diagnostic and prognostic value in tissue and serum-based analyses.Finally,we discuss therapeutic opportunities and propose future directions to translate RP11-derived lncRNAs into clinically actionable biomarkers and targets for precision liver cancer therapy.展开更多
Gastric cancer(GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. Micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs) are the most popular non-coding RNAs in cancer rese...Gastric cancer(GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. Micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs) are the most popular non-coding RNAs in cancer research. To date,the roles of mi RNAs and lnc RNAs have been extensively studied in GC,suggesting that mi RNAs and lnc RNAs represent a vital component of tumor biology. Furthermore,circulating mi RNAs and lnc RNAs are found to be dysregulated in patients with GC compared with healthy individuals. Circulating mi RNAs and lnc RNAs may function as promising biomarkers to improve the early detection of GC. Multiple possibilities for mi RNA secretion have been elucidated,including active secretion by microvesicles,exosomes,apoptotic bodies,highdensity lipoproteins and protein complexes as well as passive leakage from cells. However,the mechanism underlying lnc RNA secretion and the functions of circulating mi RNAs and lnc RNAs have not been fully illuminated. Concurrently,to standardize results of global investigations of circulating mi RNAs and lnc RNAs biomarker studies,several recommendations for preanalytic considerations are put forward. In this review,we summarize the known circulating mi RNAs and lnc RNAs for GC diagnosis. The possible mechanism of mi RNA and lnc RNA secretion as well as methodologies for identification of circulating mi RNAs and lnc RNAs are also discussed. The topics covered here highlight new insights into GC diagnosis and screening.展开更多
Background:The CHA_(2)DS_(2)-VASc score was initially applied to stratify stroke risk in patients with atrial fibrillation(AF)and was found to be effective in predicting all-cause mortality outcomes.To date,it is stil...Background:The CHA_(2)DS_(2)-VASc score was initially applied to stratify stroke risk in patients with atrial fibrillation(AF)and was found to be effective in predicting all-cause mortality outcomes.To date,it is still unclear whether circulating long non-coding RNAs(lncRNAs)as emerging biomarkers,can improve the predictive power of the CHA_(2)DS_(2)-VASc score in stroke and all-cause mortality.Methods:Candidate lncRNAs were screened by searching the literature and analyzing previous RNA sequencing results.After preliminary verification in 29 patients with AF,the final selected lncRNAs were evaluated by Cox proportional hazards regression in 192 patients to determine whether their relative expression levels were associated with stroke and all-cause mortality.The c-statistic,net reclassification improvement(NRI),and integrated discrimination improvement of the patients were calculated to evaluate the discrimination and reclassification power for stroke and all-cause mortality when adding lncRNA expression levels to the CHA_(2)DS_(2)-VASc score model.Results:Five plasma lncRNAs associated with stroke and all-cause mortality in AF patients were selected in our screening process.Patients with elevated H19 levels were found to have a higher risk of stroke(hazard ratio[HR]3.264,95%confidence interval[CI]:1.364–7.813,P=0.008).Adding the H19 expression level to the CHA_(2)DS_(2)-VASc score significantly improved the discrimination and reclassification power of the CHA_(2)DS_(2)-VASc score for stroke in AF patients.In addition,the H19 level showed a marginally significant association with all-cause mortality(HR 2.263,95%CI:0.889–5.760,P=0.087),although it appeared to have no significant improvement for the CHA_(2)DS_(2)-VASc model for predicting all-cause mortality.Conclusions:Plasma expression of H19 was associated with stroke risk in AF patients and improved the discriminatory power of the CHA_(2)DS_(2)-VASc score.Therefore,lncRNA H19 served as an emerging non-invasive biomarker for stroke risk prediction in patients with AF.展开更多
Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathologica...Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathological characteristics and molecular pathways associated with its progression.Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.These non-coding RNAs regulate several biological processes critical to the advancement of the disease,offering promising potential as therapeutic targets and diagnostic biomarkers.Therefore,this review aims to investigate the underlying mechanisms of Alzheimer's disease onset,with a particular focus on microRNAs,long non-coding RNAs,and circular RNAs associated with the disease.The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs.It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease,as well as how these noncoding RNAs influence the disease's progression by regulating gene expression and protein functions.For example,miR-9 targets the UBE4B gene,promoting autophagy-mediated degradation of Tau protein,thereby reducing Tau accumulation and delaying Alzheimer's disease progression.Conversely,the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA,promoting the generation of amyloid-βand accelerating Alzheimer's disease development.Additionally,circular RNAs play significant roles in regulating neuroinflammatory responses.By integrating insights from these regulatory mechanisms,there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease.This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs,potentially paving the way for early detection and novel treatment strategies.展开更多
Hepatocellular carcinoma(HCC)is a highly lethal malignancy with limited treatment options,particularly for patients with advanced stages of the disease.Sorafenib,the standard first-line therapy,faces significant chall...Hepatocellular carcinoma(HCC)is a highly lethal malignancy with limited treatment options,particularly for patients with advanced stages of the disease.Sorafenib,the standard first-line therapy,faces significant challenges due to the development of drug resistance.Yu et al explored the mechanisms by which lncRNA KIF9-AS1 regulates the stemness and sorafenib resistance in HCC using a combination of cell culture,transfection,RNA immunoprecipitation,co-immunoprecipitation,and xenograft tumor models.They demonstrate that N6-methyladenosine-modified long non-coding RNA KIF9-AS1 acts as an oncogene in HCC.This modification involves methyltransferase-like 3 and insulin-like growth factor 2 mRNA-binding protein 1,which play critical roles in regulating KIF9-AS1.Furthermore,KIF9-AS1 stabilizes and upregulates short stature homeobox 2 by promoting its deubiquitination through ubiquitin-specific peptidase 1,thereby enhancing stemness and contributing to sorafenib resistance in HCC cells.These findings provide a theoretical basis for KIF9-AS1 as a diagnostic marker and therapeutic target for HCC,highlighting the need for further investigation into its clinical application potential.展开更多
Gastric cancer(GC)is one of the most aggressive malignancies worldwide and is characterized by its poor prognosis and resistance to conventional therapies.Autophagy and long non-coding RNAs(lncRNAs)play critical yet c...Gastric cancer(GC)is one of the most aggressive malignancies worldwide and is characterized by its poor prognosis and resistance to conventional therapies.Autophagy and long non-coding RNAs(lncRNAs)play critical yet complex roles in GC,functioning as both tumor suppressors and promoters depending on the disease stage and context.Autophagy influences cellular homeostasis and metabolism,whereas lncRNAs regulate gene expression through epigenetic modifications,RNA sponging,and protein interactions.Notably,the interplay between lncRNAs and autophagy modulates tumor progression,metastasis,chemoresistance,and the tumor microenvironment.This study explored the intricate relationship between lncRNAs and autophagy in GC,highlighting their roles in pathogenesis and treatment resistance.By addressing current knowledge gaps and proposing innovative therapeutic strategies,we have emphasized the potential of targeting this dynamic interplay for improved diagnostic and therapeutic outcomes.展开更多
Hepatocellular carcinoma(HCC)is the predominant form of primary liver cancer,accounting for 90%of all cases.Currently,early diagnosis of HCC can be achieved through serum alpha-fetoprotein detection,B-ultrasound,and c...Hepatocellular carcinoma(HCC)is the predominant form of primary liver cancer,accounting for 90%of all cases.Currently,early diagnosis of HCC can be achieved through serum alpha-fetoprotein detection,B-ultrasound,and computed tomography scanning;however,their specificity and sensitivity are suboptimal.Despite significant advancements in HCC biomarker detection,the prognosis for patients with HCC remains unfavorable due to tumor heterogeneity and limited understanding of its pathogenesis.Therefore,it is crucial to explore more sensitive HCC biomarkers for improved diagnosis,monitoring,and management of the disease.Long non-coding RNA(lncRNA)serves as an auxiliary carrier of genetic information and also plays diverse intricate regulatory roles that greatly contribute to genome complexity.Moreover,investigating gene expression regulation networks from the perspective of lncRNA may provide insights into the diagnosis and prognosis of HCC.We searched the PubMed database for literature,comprehensively classified regulated cell death mechanisms and systematically reviewed research progress on lncRNA-mediated cell death pathways in HCC cells.Furthermore,we prospectively summarize its potential implications in diagnosing and treating HCC.展开更多
Background:Long non-coding RNAs are implicated in metabolic diseases and malignancies,but their role in multiple myeloma(MM)with type 2 diabetes mellitus(T2DM)remains unclear.This study evaluated Long non-coding RNA M...Background:Long non-coding RNAs are implicated in metabolic diseases and malignancies,but their role in multiple myeloma(MM)with type 2 diabetes mellitus(T2DM)remains unclear.This study evaluated Long non-coding RNA Morrbid expression in MM patients with/without T2DM.Methods:The study enrolled 107 MM patients(48 with T2DM,59 without)and 72 non-MM controls(23 with T2DM,49 without).Peripheral blood mononuclear cells(PBMCs)were isolated from whole blood samples using red blood cell lysis.Total RNA was extracted from PBMCs,followed by reverse transcription,and the expression levels of Morrbid were detected by Reverse transcription-quantitative PCR.Results:We found that the expression of Morrbid was upregulated in the MM group compared to the non-MM patients.Within the MM group,the expression of Morrbid was significantly higher in patients with T2DM than in those without T2DM.In contrast,no significant difference in Morrbid expression was observed between T2DM and non-T2DM patients in the non-MM patients.Furthermore,we discovered a positive correlation between Morrbid expression and fasting blood sugar levels in MM patients.Operating characteristic curve analysis revealed an area under the curve of 0.822(sensitivity 77.1%,specificity 79.7%)for diagnosing T2DM in MM,suggesting that Morrbid may serve as a novel diagnostic biomarker for T2DM in MM patients.Conclusions:The high expression of Morrbid in MM patients with T2DM may indicate its critical role in tumor-related glucose metabolism.Additionally,Morrbid may potentially serve as a diagnostic biomarker for T2DM in MM patients.展开更多
BACKGROUND Spinal cord injury(SCI)is a severe and permanent trauma that often leads to significant motor,sensory,and autonomic dysfunction.Neuronal apoptosis is a major pathomechanism underlying secondary injury in SC...BACKGROUND Spinal cord injury(SCI)is a severe and permanent trauma that often leads to significant motor,sensory,and autonomic dysfunction.Neuronal apoptosis is a major pathomechanism underlying secondary injury in SCI.Long non-coding RNAs(lncRNAs)have emerged as key regulators of gene expression and cellular processes,including apoptosis.However,the role of lncRNA growth arrest-specific transcript 5(GAS5)in SCI-induced neuronal apoptosis remains unclear.AIM To investigate the role of lncRNA GAS5 in SCI-induced neuronal apoptosis via its interaction with microRNA(miR)-21 and the phosphatase and tensin homolog(PTEN)/AKT pathway.METHODS SCI rat models and hypoxic neuronal cell models were established.Motor function was assessed using the Basso-Beattie-Bresnahan score.Expression levels of GAS5,miR-21,PTEN,caspase 3,B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),and AKT were measured using quantitative PCR or Western blot analysis.Neuronal apoptosis was determined by TUNEL staining.Dual-luciferase reporter assays validated GAS5-miR-21 binding.Knockdown and overexpression experiments explored the functional effects of the GAS5/miR-21 axis.RESULTS GAS5 was significantly upregulated in the spinal cord following SCI,coinciding with increased neuronal apoptosis and decreased AKT activation.In vitro experiments demonstrated that GAS5 acted as a molecular sponge for miR-21,leading to increased PTEN expression and inhibition of the AKT signaling pathway,thereby promoting apoptosis.In vivo,GAS5 knockdown attenuated neuronal apoptosis,enhanced AKT activation,and improved motor function recovery in SCI rats.CONCLUSION GAS5 promotes neuronal apoptosis in SCI by binding to miR-21 and upregulating PTEN expression,inhibiting the AKT pathway.Targeting GAS5 may represent a novel therapeutic strategy for SCI.展开更多
Spinal cord injury(SCI),either from trauma or degenerative changes,can res ult in severe disability and impaired quality of life.Understanding the cellular processes and molecular mechanisms that underlie SCI is imper...Spinal cord injury(SCI),either from trauma or degenerative changes,can res ult in severe disability and impaired quality of life.Understanding the cellular processes and molecular mechanisms that underlie SCI is imperative to identifying molecular targets for potential therapy.Recent studies have shown that non-coding RNAs,including both long non-coding RNAs(lncRNAs)and circular RNAs(circRNAs),regulate various cellular processes in SCI.In this review,we will describe the changes in lncRNA and circRNA expression that occur after SCI and how these changes may be related to SCI progression.Current evidence for the roles of lncRNAs and circRNAs in neuronal cell death and glial cell activation will also be reviewed.Finally,the possibility that lncRNAs and circRNAs are novel modulato rs of SCI pathogenesis will be discussed.展开更多
Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic ...Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.展开更多
AIM: To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer. METHODS: Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were d...AIM: To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer. METHODS: Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were downloaded from the Gene Expression Omnibus (GEO). We re-annotated the probes of the human exon arrays and retained the probes uniquely mapping to lncRNAs at the gene level. LncRNA expression profiles were generated by using robust multi-array average method in affymetrix power tools. The normalized data were then analyzed with a Bioconductor package linear models for microarray data and genes with adjusted P -values below 0.01 were considered differentially expressed. An independent data set was used to validate the results. RESULTS: With the computational pipeline established to re-annotate over 6.5 million probes of the Affymetrix Human Exon 1.0 ST array, we identified 136053 probes uniquely mapping to lncRNAs at the gene level. These probes correspond to 9294 lncRNAs, covering nearly 76% of the GENCODE lncRNA data set. By analyzing GSE27342 consisting of 80 paired gastric cancer and normal adjacent tissue samples, we identified 88 lncRNAs that were differentially expressed in gastric cancer, some of which have been reported to play a role in cancer, such as LINC00152, taurine upregulated 1, urothelial cancer associated 1, Pvt1 oncogene, small nucleolar RNA host gene 1 and LINC00261. In the validation data set GSE33335, 59% of these differentially expressed lncRNAs showed significant expression changes (adjusted P -value < 0.01) with the same direction. CONCLUSION: We identified a set of lncRNAs differentially expressed in gastric cancer, providing useful information for discovery of new biomarkers and therapeutic targets in gastric cancer.展开更多
Long non-coding RNAs （lncRNAs） refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as...Long non-coding RNAs （lncRNAs） refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression. Different lncRNAs exist throughout the genome. LncRNAs are also known for their roles in different human diseases such as cancer. HOTAIR is an lncRNA that plays a role as an oncogenic molecule in different cancer ceils, such as breast, gastric, colorectal, and cervical cancer cells. Therefore, HOTAIR expression level is a potential biomarker for diagnostic and therapeutic purposes in several cancers. This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 （PRC2）. In this review, we describe the molecular function and regulation of HOTAIR and its role in different types of cancers.展开更多
BACKGROUND Long non-coding RNAs(lncRNAs) are widely involved in tumor regulation.Nevertheless, the role of the lncRNA cancer susceptibility 19(CASC19) in colorectal cancer(CRC) has yet to be fully clarified.AIM To exp...BACKGROUND Long non-coding RNAs(lncRNAs) are widely involved in tumor regulation.Nevertheless, the role of the lncRNA cancer susceptibility 19(CASC19) in colorectal cancer(CRC) has yet to be fully clarified.AIM To explore the effect of CASC19 on proliferation and metastasizing ability of CRC cells.METHODS CASC19 expression in human CRC tissues, pair-matched adjacent normal colon tissues, and CRC cells was detected using quantitative real-time PCR(qRT-PCR).CASC19 expression, as well as its relation to overall survival, was extrapolated by Kaplan-Meier survival analysis together with multivariable Cox regression assay.In vitro experiments were performed to confirm whether CASC19 regulates CRC cell invasion, migration, proliferation, and apoptosis.RESULTS CASC19 expression was markedly upregulated in CRC tissues and CRC cell lines(P < 0.05). qRT-PCR revealed that CASC19 expression was higher in 25 tissue samples from patients with aggressive CRC compared with the 27 tissue samples from patients with nonaggressive CRC(P < 0.05). Higher CASC19 expression was associated with poorer patient prognoses. Furthermore, in vitro experiments demonstrated that CASC19 overexpression enhanced CRC cell invasion,migration, and proliferation. CASC19 overexpression enhanced the expression of cell migration inducing hyaluronidase 1(CEMIP) and epithelial-mesenchymal transition markers. MiR-140-5 p was found to be able to bind directly to CASC19 and CEMIP. Overexpression of miR-140-5 p reversed the effect of CASC19 on cellproliferation and tumor migration, as well as suppressed CASC19-induced CEMIP expression.CONCLUSION CASC19 positively regulates CEMIP expression through targeting miR-140-5 p.CASC19 may possess an oncogenic function in CRC progression, highlighting its potential as an essential biomarker in CRC diagnosis and therapy.展开更多
BACKGROUND Esophageal cancer is a common digestive tract tumor that is generally treated with radiotherapy.Poor responses to radiotherapy in most patients generally result in local radiotherapy failure,so it is essent...BACKGROUND Esophageal cancer is a common digestive tract tumor that is generally treated with radiotherapy.Poor responses to radiotherapy in most patients generally result in local radiotherapy failure,so it is essential to find new radiosensitizers that can enhance the response of cancer cells to radiotherapy and improve the survival of esophageal cancer patients with radiation resistance.The long noncoding RNA(lncRNA)Rpph1 is highly expressed in human gastric cancer tissues,and represses breast cancer cell proliferation and tumorigenesis.However,the expression of lncRNA Rpph1 in esophageal cancer and its relationship with radio-sensitivity has not been studied.AIM To explore the value of lncRNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy.METHODS Eighty-three patients with esophageal cancer admitted to Qilu Hospital of Shandong University and 90 healthy participants who received physical examinations were collected as research participants.The expression of Rpph1 was determined by qRT-PCR.siRNA-NC and siRNA-Rpph1 were transfected into esophageal cancer cell lines,and cells without transfection were designated as the blank control group.Cell survival was tested by colony formation assays,and the levels of proteins related to apoptosis and epithelial-mesenchymal transitions were determined by Western blot assays.Cell proliferation was assessed by MTT assays,cell apoptosis by flow cytometry,and cell migration by wound-healing assays.Changes in cell cycle distribution were monitored.RESULTS Rpph1 was highly expressed in esophageal carcinoma,making it a promising marker for the diagnosis of esophageal cancer.Rpph1 could also be used to distinguish different short-term responses,T stages,N stages,and clinical stages of esophageal cancer patients.The results of 3-year overall survival favored patients with lower Rpph1 expression over patients with higher Rpph1 expression(P<0.05).In vitro and in vivo experiments showed that silencing Rpph1 expression led to higher sensitivity of esophageal cancer cells to radiotherapy,stronger apoptosis in esophageal cancer cells induced by radiotherapy,higher expression of Bax and caspase-3,and lower expression of Bcl-2(Bax,caspase-3,and Bcl-2 are apoptosis-related proteins).Additionally,silencing Rpph1 attenuated radiation-induced G2/M phase arrest,and significantly inhibited the expression of proteins involved in cell proliferation,migration,and epithelial-mesenchymal transition regulation in esophageal cancer cells.CONCLUSION Rpph1 is highly expressed in esophageal cancer.Silencing Rpph1 expression can promote cell apoptosis,inhibit cell proliferation and migration,and increase radio-sensitivity.展开更多
BACKGROUND Recent evidence shows that long non-coding RNAs(lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma(HCC). Increasing studies demonstrate that lncRNAs are ...BACKGROUND Recent evidence shows that long non-coding RNAs(lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma(HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival(OS) of HCC, but the results varied. Thus,more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC.AIM To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC.METHODS Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival(RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator(LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas(TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed.RESULTS The lncRNA signature consisted of six lncRNAs: MSC-AS1, POLR2 J4, EIF3 J-AS1,SERHL, RMST, and PVT1. This risk model was significantly associated with the RFS of HCC in the TCGA cohort with a hazard ratio(HR) being 1.807(95%CI[confidence interval]: 1.329-2.457) and log-rank P-value being less than 0.001. The best candidates of the six-lncRNA signature were younger male patients with HBV infection in relatively early tumor-stage and better physical condition but with higher preoperative alpha-fetoprotein. All the lncRNAs were significantly upregulated in tumor samples compared to non-tumor samples(P < 0.05). The most significantly enriched pathways of the lncRNAs were TGF-β signaling pathway, cellular apoptosis-associated pathways, etc. The nomogram showed great utility of the lncRNA signature in HCC recurrence risk stratification.CONCLUSION We have constructed a six-lncRNA signature for prognosis prediction of HCC.This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.展开更多
Hepatocellular carcinoma(HCC) is one of the most common and aggressive cancers worldwide. HCC is the fifth common malignancy in the world and the second leading cause of cancer death in Asia. Long non-coding RNAs(lncR...Hepatocellular carcinoma(HCC) is one of the most common and aggressive cancers worldwide. HCC is the fifth common malignancy in the world and the second leading cause of cancer death in Asia. Long non-coding RNAs(lncRNAs) are RNAs with a length greater than 200 nucleotides that do not encode proteins. lncRNAs can regulate gene expression and protein synthesis in several ways by interacting with DNA, RNA and proteins in a sequence specific manner. They could regulate cellular and developmental processes through either gene inhibition or gene activation. Many studies have shown that dysregulation of lncRNAs is related to many human diseases such as cardiovascular diseases, genetic disorders, neurological diseases, immune mediated disorders and cancers. However, the study of lncRNAs is challenging as they are poorly conserved between species, their expression levels aren't as high as that of m RNAs and have great interpatient variations. The study of lncRNAs expression in cancers have been a breakthrough as it unveils potential biomarkers and drug targets for cancer therapy and helps understand the mechanism of pathogenesis. This review discusses many long non-coding RNAs and their contribution in HCC, their role in development, metastasis, and prognosis of HCC and how to regulate and target these lncRNAs as a therapeutic tool in HCC treatment in the future.展开更多
AIM To construct a long non-coding RNA(lnc RNA) signature for predicting hepatocellular carcinoma(HCC) prognosis with high efficiency.METHODS Differentially expressed lnc RNAs(DELs) between HCC specimens and peritumor...AIM To construct a long non-coding RNA(lnc RNA) signature for predicting hepatocellular carcinoma(HCC) prognosis with high efficiency.METHODS Differentially expressed lnc RNAs(DELs) between HCC specimens and peritumor liver specimens were identified using the edge R package to analyze The Cancer Genome Atlas(TCGA) LIHC dataset.Univariate Cox proportional hazards regression was performed to obtain the DELs significantly associated with overall survival(OS) in a training set.These OS-related DELs were further analyzed using a stepwise multivariate Cox regression model.Those lnc RNAs fitted in the multivariate Cox regression model and independently associated with overall survival were chosen to build a prognostic risk formula.The prognostic value ofthis formula was then validated in the test group and the entire cohort and further compared with two previously identified prognostic signatures for HCC.Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the potential biological functions of the lnc RNAs in the signature.RESULTS Based on lnc RNA expression profiling of 370 HCC patients from the TCGA database,we constructed a 5-lnc RNA signature(AC015908.3,AC091057.3,TMCC1-AS1,DCST1-AS1 and FOXD2-AS1) that was significantly associated with prognosis.HCC patients with high-risk scores based on the expression of the 5 lnc RNAs had significantly shorter survival times compared to patients with low-risk scores in both the training and test groups.Multivariate Cox regression analysis demonstrated that the prognostic value of the 5 lnc RNAs was independent of clinicopathological parameters.A comparison study involving two previously identified prognostic signatures for HCC demonstrated that this 5-lnc RNA signature showed improved prognostic power compared with the other two signatures.Functional enrichment analysis indicated that the 5 lnc RNAs were potentially involved in metabolic processes,fibrinolysis and complement activation.CONCLUSION Our present study constructed a 5-lnc RNA signature that improves survival prediction and can be used as a prognostic biomarker for HCC patients.展开更多
Summary： This study aimed to examine the effect of long non-coding RNA （LncRNA） MEG3 on the biological behaviors of renal cell carcinoma （RCC） cells 786-0 and the possible mechanism. MEG3 expression levels were d...Summary： This study aimed to examine the effect of long non-coding RNA （LncRNA） MEG3 on the biological behaviors of renal cell carcinoma （RCC） cells 786-0 and the possible mechanism. MEG3 expression levels were detected by RT-qPCR in Rmaor tissues and adjacent non-tumor tissues from 29 RCC patients and in RCC lines 786-0 and SN12 and human embryonic kidney cell line 293T. Plasmids GV144-MEG3 （MEG3 overexpression plasmid） and GV144 （control plasmid） were stably transfected into 786-0 cells by using lipofectamine 2000. Cell viabilities were determined by MTT, cell apoptosis rates by flow cytometry following PE Annexin V and 7AAD staining, apoptosis-related protein expressions by Western blotting, and Bcl-2 mRNA by RT-qPCR in the transfected cells. The results showed that MEG3 was evidently downregulated in RCC tissues （P〈0.05） and RCC cell lines （P〈0.05）. The viabilities of 786-0 cells were decreased significantly after transfection with GV144-MEG3 for over 24 h （P〈0.05）. Consistently, the apoptosis rate was significantly increased in 786-0 cells transfected with GV144-MEG3 for 48 h （P〈0.05）. Furthermore, overexpression of MEG3 could reduce the expression of Bcl-2 and procaspase-9 proteins, enhance the expression of cleaved caspase-9 protein, and promote the release of cytochrome c protein to cytoplasm （P〈0.05）. Additionally, Bcl-2 mRNA level was declined by MEG3 overexpression （P〈0.05）. It was concluded that MEG3 induces the apoptosis of RCC cells possibly by activating the mitochondrial pathway.展开更多
基金Supported by the National Research,Development and Innovation Office,No.NVKP_16-1-2016-0004
文摘Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.
基金supported by the National Research Foundation of Korea(NRF),funded by the Ministry of Science and ICT(MSIT),Republic of Korea(grant numbers:RS-2022-NR070489 and RS-2023-00210847)the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health and Welfare,Republic of Korea(grant number HR21C1003).
文摘Hepatocellular carcinoma(HCC)remains one of the most prevalent and lethal malignancies worldwide.Long non-coding RNAs(lncRNAs)have emerged as crucial regulators of gene expression and cancer progression,yet the functional diversity of RP11-derived lncRNAs—originally mapped to bacterial artificial chromosome(BAC)clones from the Roswell Park Cancer Institute—has only recently begun to be appreciated.This mini-review aims to systematically synthesize current findings on RP11-derived lncRNAs in HCC,outlining their genomic origins,molecular mechanisms,and biological significance.We highlight their roles in metabolic reprogramming,microRNA network modulation,and tumor progression,as well as their diagnostic and prognostic value in tissue and serum-based analyses.Finally,we discuss therapeutic opportunities and propose future directions to translate RP11-derived lncRNAs into clinically actionable biomarkers and targets for precision liver cancer therapy.
文摘Gastric cancer(GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. Micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs) are the most popular non-coding RNAs in cancer research. To date,the roles of mi RNAs and lnc RNAs have been extensively studied in GC,suggesting that mi RNAs and lnc RNAs represent a vital component of tumor biology. Furthermore,circulating mi RNAs and lnc RNAs are found to be dysregulated in patients with GC compared with healthy individuals. Circulating mi RNAs and lnc RNAs may function as promising biomarkers to improve the early detection of GC. Multiple possibilities for mi RNA secretion have been elucidated,including active secretion by microvesicles,exosomes,apoptotic bodies,highdensity lipoproteins and protein complexes as well as passive leakage from cells. However,the mechanism underlying lnc RNA secretion and the functions of circulating mi RNAs and lnc RNAs have not been fully illuminated. Concurrently,to standardize results of global investigations of circulating mi RNAs and lnc RNAs biomarker studies,several recommendations for preanalytic considerations are put forward. In this review,we summarize the known circulating mi RNAs and lnc RNAs for GC diagnosis. The possible mechanism of mi RNA and lnc RNA secretion as well as methodologies for identification of circulating mi RNAs and lnc RNAs are also discussed. The topics covered here highlight new insights into GC diagnosis and screening.
文摘Background:The CHA_(2)DS_(2)-VASc score was initially applied to stratify stroke risk in patients with atrial fibrillation(AF)and was found to be effective in predicting all-cause mortality outcomes.To date,it is still unclear whether circulating long non-coding RNAs(lncRNAs)as emerging biomarkers,can improve the predictive power of the CHA_(2)DS_(2)-VASc score in stroke and all-cause mortality.Methods:Candidate lncRNAs were screened by searching the literature and analyzing previous RNA sequencing results.After preliminary verification in 29 patients with AF,the final selected lncRNAs were evaluated by Cox proportional hazards regression in 192 patients to determine whether their relative expression levels were associated with stroke and all-cause mortality.The c-statistic,net reclassification improvement(NRI),and integrated discrimination improvement of the patients were calculated to evaluate the discrimination and reclassification power for stroke and all-cause mortality when adding lncRNA expression levels to the CHA_(2)DS_(2)-VASc score model.Results:Five plasma lncRNAs associated with stroke and all-cause mortality in AF patients were selected in our screening process.Patients with elevated H19 levels were found to have a higher risk of stroke(hazard ratio[HR]3.264,95%confidence interval[CI]:1.364–7.813,P=0.008).Adding the H19 expression level to the CHA_(2)DS_(2)-VASc score significantly improved the discrimination and reclassification power of the CHA_(2)DS_(2)-VASc score for stroke in AF patients.In addition,the H19 level showed a marginally significant association with all-cause mortality(HR 2.263,95%CI:0.889–5.760,P=0.087),although it appeared to have no significant improvement for the CHA_(2)DS_(2)-VASc model for predicting all-cause mortality.Conclusions:Plasma expression of H19 was associated with stroke risk in AF patients and improved the discriminatory power of the CHA_(2)DS_(2)-VASc score.Therefore,lncRNA H19 served as an emerging non-invasive biomarker for stroke risk prediction in patients with AF.
文摘Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathological characteristics and molecular pathways associated with its progression.Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.These non-coding RNAs regulate several biological processes critical to the advancement of the disease,offering promising potential as therapeutic targets and diagnostic biomarkers.Therefore,this review aims to investigate the underlying mechanisms of Alzheimer's disease onset,with a particular focus on microRNAs,long non-coding RNAs,and circular RNAs associated with the disease.The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs.It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease,as well as how these noncoding RNAs influence the disease's progression by regulating gene expression and protein functions.For example,miR-9 targets the UBE4B gene,promoting autophagy-mediated degradation of Tau protein,thereby reducing Tau accumulation and delaying Alzheimer's disease progression.Conversely,the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA,promoting the generation of amyloid-βand accelerating Alzheimer's disease development.Additionally,circular RNAs play significant roles in regulating neuroinflammatory responses.By integrating insights from these regulatory mechanisms,there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease.This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs,potentially paving the way for early detection and novel treatment strategies.
基金Supported by National Natural Science Foundation of China,No.82405223Yunling Scholars Program,No.XDYC-YLXZ-2022-0027.
文摘Hepatocellular carcinoma(HCC)is a highly lethal malignancy with limited treatment options,particularly for patients with advanced stages of the disease.Sorafenib,the standard first-line therapy,faces significant challenges due to the development of drug resistance.Yu et al explored the mechanisms by which lncRNA KIF9-AS1 regulates the stemness and sorafenib resistance in HCC using a combination of cell culture,transfection,RNA immunoprecipitation,co-immunoprecipitation,and xenograft tumor models.They demonstrate that N6-methyladenosine-modified long non-coding RNA KIF9-AS1 acts as an oncogene in HCC.This modification involves methyltransferase-like 3 and insulin-like growth factor 2 mRNA-binding protein 1,which play critical roles in regulating KIF9-AS1.Furthermore,KIF9-AS1 stabilizes and upregulates short stature homeobox 2 by promoting its deubiquitination through ubiquitin-specific peptidase 1,thereby enhancing stemness and contributing to sorafenib resistance in HCC cells.These findings provide a theoretical basis for KIF9-AS1 as a diagnostic marker and therapeutic target for HCC,highlighting the need for further investigation into its clinical application potential.
文摘Gastric cancer(GC)is one of the most aggressive malignancies worldwide and is characterized by its poor prognosis and resistance to conventional therapies.Autophagy and long non-coding RNAs(lncRNAs)play critical yet complex roles in GC,functioning as both tumor suppressors and promoters depending on the disease stage and context.Autophagy influences cellular homeostasis and metabolism,whereas lncRNAs regulate gene expression through epigenetic modifications,RNA sponging,and protein interactions.Notably,the interplay between lncRNAs and autophagy modulates tumor progression,metastasis,chemoresistance,and the tumor microenvironment.This study explored the intricate relationship between lncRNAs and autophagy in GC,highlighting their roles in pathogenesis and treatment resistance.By addressing current knowledge gaps and proposing innovative therapeutic strategies,we have emphasized the potential of targeting this dynamic interplay for improved diagnostic and therapeutic outcomes.
基金Supported by Science Project of Hunan Provincial Healthy Commission,No.20230844.
文摘Hepatocellular carcinoma(HCC)is the predominant form of primary liver cancer,accounting for 90%of all cases.Currently,early diagnosis of HCC can be achieved through serum alpha-fetoprotein detection,B-ultrasound,and computed tomography scanning;however,their specificity and sensitivity are suboptimal.Despite significant advancements in HCC biomarker detection,the prognosis for patients with HCC remains unfavorable due to tumor heterogeneity and limited understanding of its pathogenesis.Therefore,it is crucial to explore more sensitive HCC biomarkers for improved diagnosis,monitoring,and management of the disease.Long non-coding RNA(lncRNA)serves as an auxiliary carrier of genetic information and also plays diverse intricate regulatory roles that greatly contribute to genome complexity.Moreover,investigating gene expression regulation networks from the perspective of lncRNA may provide insights into the diagnosis and prognosis of HCC.We searched the PubMed database for literature,comprehensively classified regulated cell death mechanisms and systematically reviewed research progress on lncRNA-mediated cell death pathways in HCC cells.Furthermore,we prospectively summarize its potential implications in diagnosing and treating HCC.
基金Luzhou Municipal Government-Southwest Medical University Cooperation Application Foundation(Project No.:2023LZXNYDJ045)Luzhou Science and Technology Bureau,China(Project No.:2024JYJ064)Academic Research Projects of Southwest Medical University(Project No.:2023QN042&2024ZKY040)。
文摘Background:Long non-coding RNAs are implicated in metabolic diseases and malignancies,but their role in multiple myeloma(MM)with type 2 diabetes mellitus(T2DM)remains unclear.This study evaluated Long non-coding RNA Morrbid expression in MM patients with/without T2DM.Methods:The study enrolled 107 MM patients(48 with T2DM,59 without)and 72 non-MM controls(23 with T2DM,49 without).Peripheral blood mononuclear cells(PBMCs)were isolated from whole blood samples using red blood cell lysis.Total RNA was extracted from PBMCs,followed by reverse transcription,and the expression levels of Morrbid were detected by Reverse transcription-quantitative PCR.Results:We found that the expression of Morrbid was upregulated in the MM group compared to the non-MM patients.Within the MM group,the expression of Morrbid was significantly higher in patients with T2DM than in those without T2DM.In contrast,no significant difference in Morrbid expression was observed between T2DM and non-T2DM patients in the non-MM patients.Furthermore,we discovered a positive correlation between Morrbid expression and fasting blood sugar levels in MM patients.Operating characteristic curve analysis revealed an area under the curve of 0.822(sensitivity 77.1%,specificity 79.7%)for diagnosing T2DM in MM,suggesting that Morrbid may serve as a novel diagnostic biomarker for T2DM in MM patients.Conclusions:The high expression of Morrbid in MM patients with T2DM may indicate its critical role in tumor-related glucose metabolism.Additionally,Morrbid may potentially serve as a diagnostic biomarker for T2DM in MM patients.
基金Supported by the Major Research Plan from the Health Commission of Hongkou District,No.2001-03Academic Subject Boosting Plan in the Shanghai Fourth People’s Hospital affiliated to Tongji University School of Medicine Shanghai,No.SY-XKZT-2020-1003.
文摘BACKGROUND Spinal cord injury(SCI)is a severe and permanent trauma that often leads to significant motor,sensory,and autonomic dysfunction.Neuronal apoptosis is a major pathomechanism underlying secondary injury in SCI.Long non-coding RNAs(lncRNAs)have emerged as key regulators of gene expression and cellular processes,including apoptosis.However,the role of lncRNA growth arrest-specific transcript 5(GAS5)in SCI-induced neuronal apoptosis remains unclear.AIM To investigate the role of lncRNA GAS5 in SCI-induced neuronal apoptosis via its interaction with microRNA(miR)-21 and the phosphatase and tensin homolog(PTEN)/AKT pathway.METHODS SCI rat models and hypoxic neuronal cell models were established.Motor function was assessed using the Basso-Beattie-Bresnahan score.Expression levels of GAS5,miR-21,PTEN,caspase 3,B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),and AKT were measured using quantitative PCR or Western blot analysis.Neuronal apoptosis was determined by TUNEL staining.Dual-luciferase reporter assays validated GAS5-miR-21 binding.Knockdown and overexpression experiments explored the functional effects of the GAS5/miR-21 axis.RESULTS GAS5 was significantly upregulated in the spinal cord following SCI,coinciding with increased neuronal apoptosis and decreased AKT activation.In vitro experiments demonstrated that GAS5 acted as a molecular sponge for miR-21,leading to increased PTEN expression and inhibition of the AKT signaling pathway,thereby promoting apoptosis.In vivo,GAS5 knockdown attenuated neuronal apoptosis,enhanced AKT activation,and improved motor function recovery in SCI rats.CONCLUSION GAS5 promotes neuronal apoptosis in SCI by binding to miR-21 and upregulating PTEN expression,inhibiting the AKT pathway.Targeting GAS5 may represent a novel therapeutic strategy for SCI.
基金the National Natural Science Foundation of China,No.81901241(to YZ)。
文摘Spinal cord injury(SCI),either from trauma or degenerative changes,can res ult in severe disability and impaired quality of life.Understanding the cellular processes and molecular mechanisms that underlie SCI is imperative to identifying molecular targets for potential therapy.Recent studies have shown that non-coding RNAs,including both long non-coding RNAs(lncRNAs)and circular RNAs(circRNAs),regulate various cellular processes in SCI.In this review,we will describe the changes in lncRNA and circRNA expression that occur after SCI and how these changes may be related to SCI progression.Current evidence for the roles of lncRNAs and circRNAs in neuronal cell death and glial cell activation will also be reviewed.Finally,the possibility that lncRNAs and circRNAs are novel modulato rs of SCI pathogenesis will be discussed.
基金supported by the National Natural Science Foundation of China,Nos.82301486(to SL)and 82071325(to FY)Medjaden Academy&Research Foundation for Young Scientists,No.MJR202310040(to SL)+2 种基金Nanjing Medical University Science and Technique Development,No.NMUB20220060(to SL)Medical Scientific Research Project of Jiangsu Commission of Health,No.ZDA2020019(to JZ)Health China Buchang Zhiyuan Public Welfare Project for Heart and Brain Health,No.HIGHER202102(to QD).
文摘Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.
文摘AIM: To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer. METHODS: Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were downloaded from the Gene Expression Omnibus (GEO). We re-annotated the probes of the human exon arrays and retained the probes uniquely mapping to lncRNAs at the gene level. LncRNA expression profiles were generated by using robust multi-array average method in affymetrix power tools. The normalized data were then analyzed with a Bioconductor package linear models for microarray data and genes with adjusted P -values below 0.01 were considered differentially expressed. An independent data set was used to validate the results. RESULTS: With the computational pipeline established to re-annotate over 6.5 million probes of the Affymetrix Human Exon 1.0 ST array, we identified 136053 probes uniquely mapping to lncRNAs at the gene level. These probes correspond to 9294 lncRNAs, covering nearly 76% of the GENCODE lncRNA data set. By analyzing GSE27342 consisting of 80 paired gastric cancer and normal adjacent tissue samples, we identified 88 lncRNAs that were differentially expressed in gastric cancer, some of which have been reported to play a role in cancer, such as LINC00152, taurine upregulated 1, urothelial cancer associated 1, Pvt1 oncogene, small nucleolar RNA host gene 1 and LINC00261. In the validation data set GSE33335, 59% of these differentially expressed lncRNAs showed significant expression changes (adjusted P -value < 0.01) with the same direction. CONCLUSION: We identified a set of lncRNAs differentially expressed in gastric cancer, providing useful information for discovery of new biomarkers and therapeutic targets in gastric cancer.
文摘Long non-coding RNAs （lncRNAs） refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression. Different lncRNAs exist throughout the genome. LncRNAs are also known for their roles in different human diseases such as cancer. HOTAIR is an lncRNA that plays a role as an oncogenic molecule in different cancer ceils, such as breast, gastric, colorectal, and cervical cancer cells. Therefore, HOTAIR expression level is a potential biomarker for diagnostic and therapeutic purposes in several cancers. This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 （PRC2）. In this review, we describe the molecular function and regulation of HOTAIR and its role in different types of cancers.
基金Supported by the National Natural Science Foundation of China,No.81570375
文摘BACKGROUND Long non-coding RNAs(lncRNAs) are widely involved in tumor regulation.Nevertheless, the role of the lncRNA cancer susceptibility 19(CASC19) in colorectal cancer(CRC) has yet to be fully clarified.AIM To explore the effect of CASC19 on proliferation and metastasizing ability of CRC cells.METHODS CASC19 expression in human CRC tissues, pair-matched adjacent normal colon tissues, and CRC cells was detected using quantitative real-time PCR(qRT-PCR).CASC19 expression, as well as its relation to overall survival, was extrapolated by Kaplan-Meier survival analysis together with multivariable Cox regression assay.In vitro experiments were performed to confirm whether CASC19 regulates CRC cell invasion, migration, proliferation, and apoptosis.RESULTS CASC19 expression was markedly upregulated in CRC tissues and CRC cell lines(P < 0.05). qRT-PCR revealed that CASC19 expression was higher in 25 tissue samples from patients with aggressive CRC compared with the 27 tissue samples from patients with nonaggressive CRC(P < 0.05). Higher CASC19 expression was associated with poorer patient prognoses. Furthermore, in vitro experiments demonstrated that CASC19 overexpression enhanced CRC cell invasion,migration, and proliferation. CASC19 overexpression enhanced the expression of cell migration inducing hyaluronidase 1(CEMIP) and epithelial-mesenchymal transition markers. MiR-140-5 p was found to be able to bind directly to CASC19 and CEMIP. Overexpression of miR-140-5 p reversed the effect of CASC19 on cellproliferation and tumor migration, as well as suppressed CASC19-induced CEMIP expression.CONCLUSION CASC19 positively regulates CEMIP expression through targeting miR-140-5 p.CASC19 may possess an oncogenic function in CRC progression, highlighting its potential as an essential biomarker in CRC diagnosis and therapy.
文摘BACKGROUND Esophageal cancer is a common digestive tract tumor that is generally treated with radiotherapy.Poor responses to radiotherapy in most patients generally result in local radiotherapy failure,so it is essential to find new radiosensitizers that can enhance the response of cancer cells to radiotherapy and improve the survival of esophageal cancer patients with radiation resistance.The long noncoding RNA(lncRNA)Rpph1 is highly expressed in human gastric cancer tissues,and represses breast cancer cell proliferation and tumorigenesis.However,the expression of lncRNA Rpph1 in esophageal cancer and its relationship with radio-sensitivity has not been studied.AIM To explore the value of lncRNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy.METHODS Eighty-three patients with esophageal cancer admitted to Qilu Hospital of Shandong University and 90 healthy participants who received physical examinations were collected as research participants.The expression of Rpph1 was determined by qRT-PCR.siRNA-NC and siRNA-Rpph1 were transfected into esophageal cancer cell lines,and cells without transfection were designated as the blank control group.Cell survival was tested by colony formation assays,and the levels of proteins related to apoptosis and epithelial-mesenchymal transitions were determined by Western blot assays.Cell proliferation was assessed by MTT assays,cell apoptosis by flow cytometry,and cell migration by wound-healing assays.Changes in cell cycle distribution were monitored.RESULTS Rpph1 was highly expressed in esophageal carcinoma,making it a promising marker for the diagnosis of esophageal cancer.Rpph1 could also be used to distinguish different short-term responses,T stages,N stages,and clinical stages of esophageal cancer patients.The results of 3-year overall survival favored patients with lower Rpph1 expression over patients with higher Rpph1 expression(P<0.05).In vitro and in vivo experiments showed that silencing Rpph1 expression led to higher sensitivity of esophageal cancer cells to radiotherapy,stronger apoptosis in esophageal cancer cells induced by radiotherapy,higher expression of Bax and caspase-3,and lower expression of Bcl-2(Bax,caspase-3,and Bcl-2 are apoptosis-related proteins).Additionally,silencing Rpph1 attenuated radiation-induced G2/M phase arrest,and significantly inhibited the expression of proteins involved in cell proliferation,migration,and epithelial-mesenchymal transition regulation in esophageal cancer cells.CONCLUSION Rpph1 is highly expressed in esophageal cancer.Silencing Rpph1 expression can promote cell apoptosis,inhibit cell proliferation and migration,and increase radio-sensitivity.
基金Supported by The National Natural Science Foundation of China,No.81773128 and No.81871998the Natural Science Basic Research Plan in Shaanxi Province of China,No.2017JM8039+1 种基金China Postdoctoral Science Foundation,No.2018m641000Research Fund for Young Star of Science and Technology in Shaanxi Province,No.2018KJXX-022
文摘BACKGROUND Recent evidence shows that long non-coding RNAs(lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma(HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival(OS) of HCC, but the results varied. Thus,more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC.AIM To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC.METHODS Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival(RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator(LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas(TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed.RESULTS The lncRNA signature consisted of six lncRNAs: MSC-AS1, POLR2 J4, EIF3 J-AS1,SERHL, RMST, and PVT1. This risk model was significantly associated with the RFS of HCC in the TCGA cohort with a hazard ratio(HR) being 1.807(95%CI[confidence interval]: 1.329-2.457) and log-rank P-value being less than 0.001. The best candidates of the six-lncRNA signature were younger male patients with HBV infection in relatively early tumor-stage and better physical condition but with higher preoperative alpha-fetoprotein. All the lncRNAs were significantly upregulated in tumor samples compared to non-tumor samples(P < 0.05). The most significantly enriched pathways of the lncRNAs were TGF-β signaling pathway, cellular apoptosis-associated pathways, etc. The nomogram showed great utility of the lncRNA signature in HCC recurrence risk stratification.CONCLUSION We have constructed a six-lncRNA signature for prognosis prediction of HCC.This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.
文摘Hepatocellular carcinoma(HCC) is one of the most common and aggressive cancers worldwide. HCC is the fifth common malignancy in the world and the second leading cause of cancer death in Asia. Long non-coding RNAs(lncRNAs) are RNAs with a length greater than 200 nucleotides that do not encode proteins. lncRNAs can regulate gene expression and protein synthesis in several ways by interacting with DNA, RNA and proteins in a sequence specific manner. They could regulate cellular and developmental processes through either gene inhibition or gene activation. Many studies have shown that dysregulation of lncRNAs is related to many human diseases such as cardiovascular diseases, genetic disorders, neurological diseases, immune mediated disorders and cancers. However, the study of lncRNAs is challenging as they are poorly conserved between species, their expression levels aren't as high as that of m RNAs and have great interpatient variations. The study of lncRNAs expression in cancers have been a breakthrough as it unveils potential biomarkers and drug targets for cancer therapy and helps understand the mechanism of pathogenesis. This review discusses many long non-coding RNAs and their contribution in HCC, their role in development, metastasis, and prognosis of HCC and how to regulate and target these lncRNAs as a therapeutic tool in HCC treatment in the future.
基金Supported by the National Nature Science Foundation of China,No.81702816(to Zhao QJ)Shandong Provincial Natural Science Foundation,No.ZR2017PH030(to Zhao QJ)
文摘AIM To construct a long non-coding RNA(lnc RNA) signature for predicting hepatocellular carcinoma(HCC) prognosis with high efficiency.METHODS Differentially expressed lnc RNAs(DELs) between HCC specimens and peritumor liver specimens were identified using the edge R package to analyze The Cancer Genome Atlas(TCGA) LIHC dataset.Univariate Cox proportional hazards regression was performed to obtain the DELs significantly associated with overall survival(OS) in a training set.These OS-related DELs were further analyzed using a stepwise multivariate Cox regression model.Those lnc RNAs fitted in the multivariate Cox regression model and independently associated with overall survival were chosen to build a prognostic risk formula.The prognostic value ofthis formula was then validated in the test group and the entire cohort and further compared with two previously identified prognostic signatures for HCC.Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the potential biological functions of the lnc RNAs in the signature.RESULTS Based on lnc RNA expression profiling of 370 HCC patients from the TCGA database,we constructed a 5-lnc RNA signature(AC015908.3,AC091057.3,TMCC1-AS1,DCST1-AS1 and FOXD2-AS1) that was significantly associated with prognosis.HCC patients with high-risk scores based on the expression of the 5 lnc RNAs had significantly shorter survival times compared to patients with low-risk scores in both the training and test groups.Multivariate Cox regression analysis demonstrated that the prognostic value of the 5 lnc RNAs was independent of clinicopathological parameters.A comparison study involving two previously identified prognostic signatures for HCC demonstrated that this 5-lnc RNA signature showed improved prognostic power compared with the other two signatures.Functional enrichment analysis indicated that the 5 lnc RNAs were potentially involved in metabolic processes,fibrinolysis and complement activation.CONCLUSION Our present study constructed a 5-lnc RNA signature that improves survival prediction and can be used as a prognostic biomarker for HCC patients.
基金supported by grants from the National Natural Science Foundation of China(Nos.81001132,81172423,and 81272816)
文摘Summary： This study aimed to examine the effect of long non-coding RNA （LncRNA） MEG3 on the biological behaviors of renal cell carcinoma （RCC） cells 786-0 and the possible mechanism. MEG3 expression levels were detected by RT-qPCR in Rmaor tissues and adjacent non-tumor tissues from 29 RCC patients and in RCC lines 786-0 and SN12 and human embryonic kidney cell line 293T. Plasmids GV144-MEG3 （MEG3 overexpression plasmid） and GV144 （control plasmid） were stably transfected into 786-0 cells by using lipofectamine 2000. Cell viabilities were determined by MTT, cell apoptosis rates by flow cytometry following PE Annexin V and 7AAD staining, apoptosis-related protein expressions by Western blotting, and Bcl-2 mRNA by RT-qPCR in the transfected cells. The results showed that MEG3 was evidently downregulated in RCC tissues （P〈0.05） and RCC cell lines （P〈0.05）. The viabilities of 786-0 cells were decreased significantly after transfection with GV144-MEG3 for over 24 h （P〈0.05）. Consistently, the apoptosis rate was significantly increased in 786-0 cells transfected with GV144-MEG3 for 48 h （P〈0.05）. Furthermore, overexpression of MEG3 could reduce the expression of Bcl-2 and procaspase-9 proteins, enhance the expression of cleaved caspase-9 protein, and promote the release of cytochrome c protein to cytoplasm （P〈0.05）. Additionally, Bcl-2 mRNA level was declined by MEG3 overexpression （P〈0.05）. It was concluded that MEG3 induces the apoptosis of RCC cells possibly by activating the mitochondrial pathway.
