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
Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effec...Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effective biomarkers are essential for prolonging patients’survival.Helicobacter pylori(H.pylori)infection represents the most significant risk factor for GC,with nearly all cases linked to this infection.Many non-coding RNAs(ncRNAs)are dysregulated in H.pylori-infected GC,indicating that ncRNAs may serve as biomarkers of early-stage GC.In this editorial,we discuss the study by Chen et al.Although previous studies have identified roles for miR-136 in gastric cancer proliferation,apoptosis,and invasion,none have specifically explored its relationship with H.pylori-associated gastric carcinogenesis.展开更多
A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiolog...A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus,one of the most common neurological conditions worldwide.In this review,we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition.Then,we outline the definition,classification,and biological role of non-coding RNAs.Subsequently,we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail.Specifically,we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus,including glymphatic pathways,neuroinflammatory processes,and neurological dysplasia,on the basis of the existing evidence.Lastly,we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.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
The intricate interactions between immune cells and tumors exert a profound influence on cancer progression and therapeutic efficacy.Within the tumor microenvironment,exosomes have emerged as pivotal mediators of inte...The intricate interactions between immune cells and tumors exert a profound influence on cancer progression and therapeutic efficacy.Within the tumor microenvironment,exosomes have emerged as pivotal mediators of intercellular communication,with their cargo of non-coding RNAs(ncRNAs)serving as key regulatory elements.This review examines the multifaceted roles of immune cell-derived exosomal ncRNAs in tumor biology.The involvement of various immune cells,including T cells,B cells,natural killer cells,macrophages,neutrophils,and myeloid-derived suppressor cells,in utilizing exosomal ncRNAs to regulate tumor initiation and progression is explored.Additionally,the biogenesis and delivery mechanisms of these immune cell-derived exosomal ncRNAs are discussed,alongside their potential clinical applications in cancer.展开更多
Matrix metalloproteinases(MMPs)are essential enzymes involved in extracellular matrix degradation and remodeling.Such processes are integral to normal tissue homeostasis and several pathological conditions such as can...Matrix metalloproteinases(MMPs)are essential enzymes involved in extracellular matrix degradation and remodeling.Such processes are integral to normal tissue homeostasis and several pathological conditions such as cancer.Among these MMPs,MMP-13 plays a key role in cancer progression,driving tumor invasion,metastasis,and angiogenesis.Despite significant advancements in understanding its biology,therapeutic targeting of MMP-13 remains challenging owing to its complex and multifaceted regulatory mechanisms.Recent studies have underscored the pivotal role of non-coding RNAs(ncRNAs),including long ncRNAs,microRNAs,and circular RNAs,in modulating MMP-13 expression.This review provides a comprehensive analysis of MMP-13 regulation by several signaling pathways,the influence of ncRNAs on these signaling pathways,and MMP-13 expression during cancer progression and metastasis.Furthermore,we explored the clinical relevance of ncRNA-mediated regulatory networks,highlighting their potential as diagnostic biomarkers and therapeutic targets in various cancers.By unraveling these regulatory mechanisms,this review offers valuable insights into innovative strategies for cancer diagnosis and treatment and emphasizes the translational significance of ncRNA-mediated MMP-13 regulation in oncology.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
Mesenchymal stem cells(MSCs)are known for their ability to differentiate into various cell lineages,including osteoblasts(bone-forming cells),and for their significant paracrine effects.Among their secreted products,e...Mesenchymal stem cells(MSCs)are known for their ability to differentiate into various cell lineages,including osteoblasts(bone-forming cells),and for their significant paracrine effects.Among their secreted products,exosomes have gained considerable attention as nanoscale carriers of bioactive molecules such as non-coding RNAs(ncRNAs).These ncRNAs,including microRNAs,long ncRNAs,and circular ncRNAs,are critical regulators of gene expression and cellular functions.Moreover,MSC-derived exosomes not only offer advantages such as targeted delivery,reduced immunogenicity,and protection of cargo material,but also carry ncRNAs that have therapeutic and diagnostic potential in bone-related disorders.Emerging evidence has highlighted the role of MSC-derived exosomal ncRNAs in osteogenesis,bone remodeling,and intercellular signaling in the bone microenvironment.This review consolidates recent research on the role of MSC-derived exosomal ncRNAs in maintaining bone homeostasis and bone-related disorders via various signaling pathways and epigenetic modifications.Furthermore,we explore the therapeutic potential of MSC-derived exosomal ncRNAs as biomarkers and therapeutic targets.This comprehensive review offers key insights into the regulatory roles of MSC-derived exosomal ncRNAs in bone biology and their clinical significance in bone-related diseases.展开更多
Lung cancer is a common cause of cancer-related death globally.The majority of lung cancer patients initially benefit from chemotherapy and immunotherapy.However,as the treatment cycle progresses and the disease evolv...Lung cancer is a common cause of cancer-related death globally.The majority of lung cancer patients initially benefit from chemotherapy and immunotherapy.However,as the treatment cycle progresses and the disease evolves,the emergence of acquired resistance leads to treatment failure.Many researches have shown that non-coding RNAs(ncRNAs)not only influence lung cancer progression but also act as potential mediators of immunotherapy and chemotherapy resistance in lung cancer,mediating drug resistance by regulating multiple targets and pathways.In addition,the regulation of immune response by ncRNAs is dualistic,forming a microenvironment for inhibits/promotes immune escape through changes in the expression of immune checkpoints.The aim of this review is to understand the effects of ncRNAs on the occurrence and development of lung cancer,focusing on the role of ncRNAs in regulating drug resistance of lung cancer.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
Autism spectrum disorder(ASD)is a neurodevelopmental disorder where de novo mutations play a significant role.Although coding mutations in ASD have been extensively characterized,the impact of non-coding de novo mutat...Autism spectrum disorder(ASD)is a neurodevelopmental disorder where de novo mutations play a significant role.Although coding mutations in ASD have been extensively characterized,the impact of non-coding de novo mutations(ncDNMs)remains less understood.Here,we integrate cortex cell-specific cis-regulatory element annotations,a deep learning-based variant prediction model,and massively parallel reporter assays to systematically evaluate the functional impact of 227,878 ncDNMs from Simons Simplex Collection(SSC)and Autism Speaks MSSNG resource(MSSNG)cohorts.Our analysis identifies 238 ncDNMs with confirmed functional regulatory effects,including 137 down-regulated regulatory mutations(DrMuts)and 101 up-regulated regulatory mutations(UrMuts).Subsequent association analyses reveal that only DrMuts regulating loss-of-function(LoF)intolerant genes rather than other ncDNMs are significantly associated with the risk of ASD(Odds ratio=4.34;P=0.001).A total of 42 potential ASD-risk DrMuts across 41 candidate ASD-susceptibility genes are identified,including 12 recognized and 29 unreported genes.Interestingly,these noncoding disruptive mutations tend to be observed in genes extremely intolerant to LoF mutations.Our study introduces an optimized approach for elucidating the functional roles of ncDNMs,thereby expanding the spectrum of pathogenic variants and deepening our understanding of the complex molecular mechanisms underlying ASD.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
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
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
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
Non-coding RNAs(ncRNAs)play key roles in development,proliferation,differentiation and apoptosis.Altered ncRNA expression is associated with gastric cancer occurrence,invasion,and metastasis.Moreover,aberrant expressi...Non-coding RNAs(ncRNAs)play key roles in development,proliferation,differentiation and apoptosis.Altered ncRNA expression is associated with gastric cancer occurrence,invasion,and metastasis.Moreover,aberrant expression of microRNAs(miRNAs)is significantly related to gastric cancer tumor stage,size,differentiation and metastasis.MiRNAs interrupt cellular signaling pathways,inhibit the activity of tumor suppressor genes,and affect the cell cycle in gastric cancer cells.Some miRNAs,including miR-21,miR-106a and miR-421,could be potential markers for the diagnosis of gastric cancer.Long non-coding RNAs (lncRNAs),a new research hotspot among cancerassociated ncRNAs,play important roles in epigenetic,transcriptional and post-transcriptional regulation.Several gastric cancer-associated lncRNAs,such as CCAT1,GACAT1,H19,and SUMO1P3,have been explored.In addition,Piwi-interacting RNAs,another type of small ncRNA that is recognized by gastroenterologists,are involved in gastric carcinogenesis,and piR-651/823represents an efficient diagnostic biomarker of gastric cancer that can be detected in the blood and gastric juice.Small interfering RNAs also function in posttranscriptional regulation in gastric cancer and might be useful in gastric cancer treatment.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
Hepatitis C virus(HCV)infection is one of main causes of hepatocellular carcinoma(HCC)and the prevalence of HCV-associated HCC is on the rise worldwide.It is particularly important and helpful to identify potential ma...Hepatitis C virus(HCV)infection is one of main causes of hepatocellular carcinoma(HCC)and the prevalence of HCV-associated HCC is on the rise worldwide.It is particularly important and helpful to identify potential markers for screening and early diagnosis of HCC among high-risk individuals with chronic hepatitis C,and to identify target molecules for the prevention and treatment of HCV-associated-HCC.Small noncoding RNAs,mainly microRNAs(miRNAs),and long non-coding RNAs(lncRNAs)with size greater than 200nucleotides,are likely to play important roles in a variety of biological processes,including development and progression of HCC.For the most part their underlying mechanisms of action remain largely unknown.In recent years,with the advance of high-resolution of microarray and application of next generation sequencing techniques,a significant number of non-coding RNAs(ncRNAs)associated with HCC,particularly caused by HCV infection,have been found to be differentially expressed and to be involved in pathogenesis of HCVassociated HCC.In this review,we focus on recent studies of ncRNAs,especially miRNAs and lncRNAs related to HCV-induced HCC.We summarize those ncRNAs aberrantly expressed in HCV-associated HCC and highlight the potential uses of ncRNAs in early detection,diagnosis and therapy of HCV-associated HCC.We also discuss the limitations of recent studies,and suggest future directions for research in the field.miRNAs,lncRNAs and their target genes may represent new candidate molecules for the prevention,diagnosis and treatment of HCC in patients with HCV infection.Studies of the potential uses of miRNAs and lncRNAs as diagnostic tools or therapies are still in their infancy.展开更多
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 The Joint Fund of Zhejiang Provincial Natural Science Foundation of China,No.LKLY25H160002.
文摘Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effective biomarkers are essential for prolonging patients’survival.Helicobacter pylori(H.pylori)infection represents the most significant risk factor for GC,with nearly all cases linked to this infection.Many non-coding RNAs(ncRNAs)are dysregulated in H.pylori-infected GC,indicating that ncRNAs may serve as biomarkers of early-stage GC.In this editorial,we discuss the study by Chen et al.Although previous studies have identified roles for miR-136 in gastric cancer proliferation,apoptosis,and invasion,none have specifically explored its relationship with H.pylori-associated gastric carcinogenesis.
基金supported by the National Natural Science Foundation of China,Nos.82171347,82371362the Natural Science Foundation of Hunan Province,No.2022JJ30971the Scientific Research Project of Hunan Provincial Health Commission of China,No.202204040024(all to GX).
文摘A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus,one of the most common neurological conditions worldwide.In this review,we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition.Then,we outline the definition,classification,and biological role of non-coding RNAs.Subsequently,we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail.Specifically,we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus,including glymphatic pathways,neuroinflammatory processes,and neurological dysplasia,on the basis of the existing evidence.Lastly,we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.
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.
基金supported by the National Natural Science Foundation of China(No.82203056)the Natural Science Foundation of Liaoning Province(No.2023-BS-167)+1 种基金the Science and Technology Talent Innovation Support Plan of Dalian(NO.2022RQ091)the“1+X”program for Clinical Competency enhancement-Clinical Research Incubation Project of the Second Hospital of Dalian Medical University(No.2022LCYJYB01)。
文摘The intricate interactions between immune cells and tumors exert a profound influence on cancer progression and therapeutic efficacy.Within the tumor microenvironment,exosomes have emerged as pivotal mediators of intercellular communication,with their cargo of non-coding RNAs(ncRNAs)serving as key regulatory elements.This review examines the multifaceted roles of immune cell-derived exosomal ncRNAs in tumor biology.The involvement of various immune cells,including T cells,B cells,natural killer cells,macrophages,neutrophils,and myeloid-derived suppressor cells,in utilizing exosomal ncRNAs to regulate tumor initiation and progression is explored.Additionally,the biogenesis and delivery mechanisms of these immune cell-derived exosomal ncRNAs are discussed,alongside their potential clinical applications in cancer.
基金Supported by the Anusandhan National Research Foundation,No.CRG/2023/000212.
文摘Matrix metalloproteinases(MMPs)are essential enzymes involved in extracellular matrix degradation and remodeling.Such processes are integral to normal tissue homeostasis and several pathological conditions such as cancer.Among these MMPs,MMP-13 plays a key role in cancer progression,driving tumor invasion,metastasis,and angiogenesis.Despite significant advancements in understanding its biology,therapeutic targeting of MMP-13 remains challenging owing to its complex and multifaceted regulatory mechanisms.Recent studies have underscored the pivotal role of non-coding RNAs(ncRNAs),including long ncRNAs,microRNAs,and circular RNAs,in modulating MMP-13 expression.This review provides a comprehensive analysis of MMP-13 regulation by several signaling pathways,the influence of ncRNAs on these signaling pathways,and MMP-13 expression during cancer progression and metastasis.Furthermore,we explored the clinical relevance of ncRNA-mediated regulatory networks,highlighting their potential as diagnostic biomarkers and therapeutic targets in various cancers.By unraveling these regulatory mechanisms,this review offers valuable insights into innovative strategies for cancer diagnosis and treatment and emphasizes the translational significance of ncRNA-mediated MMP-13 regulation in oncology.
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Supported by Anusandhan National Research Foundation,No.CRG/2023/000212.
文摘Mesenchymal stem cells(MSCs)are known for their ability to differentiate into various cell lineages,including osteoblasts(bone-forming cells),and for their significant paracrine effects.Among their secreted products,exosomes have gained considerable attention as nanoscale carriers of bioactive molecules such as non-coding RNAs(ncRNAs).These ncRNAs,including microRNAs,long ncRNAs,and circular ncRNAs,are critical regulators of gene expression and cellular functions.Moreover,MSC-derived exosomes not only offer advantages such as targeted delivery,reduced immunogenicity,and protection of cargo material,but also carry ncRNAs that have therapeutic and diagnostic potential in bone-related disorders.Emerging evidence has highlighted the role of MSC-derived exosomal ncRNAs in osteogenesis,bone remodeling,and intercellular signaling in the bone microenvironment.This review consolidates recent research on the role of MSC-derived exosomal ncRNAs in maintaining bone homeostasis and bone-related disorders via various signaling pathways and epigenetic modifications.Furthermore,we explore the therapeutic potential of MSC-derived exosomal ncRNAs as biomarkers and therapeutic targets.This comprehensive review offers key insights into the regulatory roles of MSC-derived exosomal ncRNAs in bone biology and their clinical significance in bone-related diseases.
文摘Lung cancer is a common cause of cancer-related death globally.The majority of lung cancer patients initially benefit from chemotherapy and immunotherapy.However,as the treatment cycle progresses and the disease evolves,the emergence of acquired resistance leads to treatment failure.Many researches have shown that non-coding RNAs(ncRNAs)not only influence lung cancer progression but also act as potential mediators of immunotherapy and chemotherapy resistance in lung cancer,mediating drug resistance by regulating multiple targets and pathways.In addition,the regulation of immune response by ncRNAs is dualistic,forming a microenvironment for inhibits/promotes immune escape through changes in the expression of immune checkpoints.The aim of this review is to understand the effects of ncRNAs on the occurrence and development of lung cancer,focusing on the role of ncRNAs in regulating drug resistance of lung cancer.
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supported by the National Natural Science of China(82322032 and 82221005)the Outstanding Youth Foundation of Jiangsu Province(BK20220050)+4 种基金the National Key Research&Development(R&D)Program of China(2024YFC2706800 and 2021YFC2700600)the Major Project of Changzhou Medical Center(CZKY1040101)the Major Project of Taizhou Clinical Medical College(TZKY20240003)the Major Program of Gusu School(GSKY20210102)the China Postdoctoral Science Foundation(2024M760296).
文摘Autism spectrum disorder(ASD)is a neurodevelopmental disorder where de novo mutations play a significant role.Although coding mutations in ASD have been extensively characterized,the impact of non-coding de novo mutations(ncDNMs)remains less understood.Here,we integrate cortex cell-specific cis-regulatory element annotations,a deep learning-based variant prediction model,and massively parallel reporter assays to systematically evaluate the functional impact of 227,878 ncDNMs from Simons Simplex Collection(SSC)and Autism Speaks MSSNG resource(MSSNG)cohorts.Our analysis identifies 238 ncDNMs with confirmed functional regulatory effects,including 137 down-regulated regulatory mutations(DrMuts)and 101 up-regulated regulatory mutations(UrMuts).Subsequent association analyses reveal that only DrMuts regulating loss-of-function(LoF)intolerant genes rather than other ncDNMs are significantly associated with the risk of ASD(Odds ratio=4.34;P=0.001).A total of 42 potential ASD-risk DrMuts across 41 candidate ASD-susceptibility genes are identified,including 12 recognized and 29 unreported genes.Interestingly,these noncoding disruptive mutations tend to be observed in genes extremely intolerant to LoF mutations.Our study introduces an optimized approach for elucidating the functional roles of ncDNMs,thereby expanding the spectrum of pathogenic variants and deepening our understanding of the complex molecular mechanisms underlying ASD.
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.
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.
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.
基金Supported by National Natural Science Foundation of China,No.81171660Zhejiang Provincial Natural Science Foundation of China,No.Y14C060003+4 种基金Natural Science Foundation of Ningbo,No.2012A610207The Scientific Innovation Team Project of Ningbo,No.2011B82014The Project of Key Disciplines in Ningbo,No.XKL11D2127 and No.XKL11D2128Foundation of Zhejiang Provincial Key Laboratory of Pathophysiology,No.201301K.C.Wong Magna Fund in Ningbo University
文摘Non-coding RNAs(ncRNAs)play key roles in development,proliferation,differentiation and apoptosis.Altered ncRNA expression is associated with gastric cancer occurrence,invasion,and metastasis.Moreover,aberrant expression of microRNAs(miRNAs)is significantly related to gastric cancer tumor stage,size,differentiation and metastasis.MiRNAs interrupt cellular signaling pathways,inhibit the activity of tumor suppressor genes,and affect the cell cycle in gastric cancer cells.Some miRNAs,including miR-21,miR-106a and miR-421,could be potential markers for the diagnosis of gastric cancer.Long non-coding RNAs (lncRNAs),a new research hotspot among cancerassociated ncRNAs,play important roles in epigenetic,transcriptional and post-transcriptional regulation.Several gastric cancer-associated lncRNAs,such as CCAT1,GACAT1,H19,and SUMO1P3,have been explored.In addition,Piwi-interacting RNAs,another type of small ncRNA that is recognized by gastroenterologists,are involved in gastric carcinogenesis,and piR-651/823represents an efficient diagnostic biomarker of gastric cancer that can be detected in the blood and gastric juice.Small interfering RNAs also function in posttranscriptional regulation in gastric cancer and might be useful in gastric cancer treatment.
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 A grant from the NIH/NHLBI,No.HL117199Institutional funds from the Carolinas Health Care Foundation and Carolinas Medical Center
文摘Hepatitis C virus(HCV)infection is one of main causes of hepatocellular carcinoma(HCC)and the prevalence of HCV-associated HCC is on the rise worldwide.It is particularly important and helpful to identify potential markers for screening and early diagnosis of HCC among high-risk individuals with chronic hepatitis C,and to identify target molecules for the prevention and treatment of HCV-associated-HCC.Small noncoding RNAs,mainly microRNAs(miRNAs),and long non-coding RNAs(lncRNAs)with size greater than 200nucleotides,are likely to play important roles in a variety of biological processes,including development and progression of HCC.For the most part their underlying mechanisms of action remain largely unknown.In recent years,with the advance of high-resolution of microarray and application of next generation sequencing techniques,a significant number of non-coding RNAs(ncRNAs)associated with HCC,particularly caused by HCV infection,have been found to be differentially expressed and to be involved in pathogenesis of HCVassociated HCC.In this review,we focus on recent studies of ncRNAs,especially miRNAs and lncRNAs related to HCV-induced HCC.We summarize those ncRNAs aberrantly expressed in HCV-associated HCC and highlight the potential uses of ncRNAs in early detection,diagnosis and therapy of HCV-associated HCC.We also discuss the limitations of recent studies,and suggest future directions for research in the field.miRNAs,lncRNAs and their target genes may represent new candidate molecules for the prevention,diagnosis and treatment of HCC in patients with HCV infection.Studies of the potential uses of miRNAs and lncRNAs as diagnostic tools or therapies are still in their infancy.
