The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research...The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research,Vol.26,No.1,2018,pp.131–143.展开更多
The published article titled“Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression inNon-Small Cell Lung Cancer”has been retracted fromOncology Research,Vol.25,No.6,2017,pp.1027–1037.DOI...The published article titled“Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression inNon-Small Cell Lung Cancer”has been retracted fromOncology Research,Vol.25,No.6,2017,pp.1027–1037.DOI:10.3727/096504016X14822800040451 URL:https://www.techscience.com/or/v25n6/56885 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.展开更多
BACKGROUND Colorectal cancer(CRC)is the second most prevalent cause of cancer-related mortality and is increasing in younger individuals.Chemotherapy,a crucial adjuvant systemic therapy for CRC management,often leads ...BACKGROUND Colorectal cancer(CRC)is the second most prevalent cause of cancer-related mortality and is increasing in younger individuals.Chemotherapy,a crucial adjuvant systemic therapy for CRC management,often leads to resistance through poorly characterized underlying molecular mechanisms.The long noncoding RNA SNHG5 is highly expressed in CRC and promotes tumor proliferation and invasion,prompting us to hypothesize that SNHG5 may play a crucial role in the chemotherapeutic agent 5-fluorouracil(5-Fu)resistance in CRC.AIM To identify the function and mechanism of SNHG5 in 5-Fu resistance in CRC.METHODS Quantitative real-time polymerase chain reaction was performed to examine the expression of SNHG5 in CRC tissues from 225-Fu-sensitive patients and 145-Fu-resistant patients and in CRC cells and 5-Fu-resistant CRC cells.Cell viability and apoptosis were assessed in SNHG5-overexpressing CRC cells and SNHG5-knockdown 5-Furesistant CRC cells.SNHG5 function in 5-Fu resistance in CRC was further analyzed using a xenograft mouse model.SNHG5 interactions with microRNAs were predicted by bioinformatics analysis.Luciferase reporter and RNA immunoprecipitation assays were performed to verify the binding between SNHG5 and miR-26b.Rescue experiments were performed to validate the functional interaction between SNHG5 and the miR-26b/p-glycoprotein(Pgp)axis.RESULTS SNHG5 expression was upregulated in 5-Fu-resistant CRC tissues and 5-Fu-resistant CRC cells.In vitro functional experiments demonstrated that SNHG5 overexpression significantly reduced cell apoptosis and enhanced cell viability,whereas SNHG5 knockdown in 5-Fu-resistant CRC cells increased cell apoptosis and decreased cell viability upon 5-Fu treatment.In a xenograft mouse model,we confirmed that SNHG5 overexpression led to a reduction in 5-Fu sensitivity in CRC in vivo.Mechanistically,SNHG5 acted as a molecular sponge for miR-26b.Rescue experiments validated that SNHG5 conferred 5-Fu resistance in CRC by regulating the miR-26b/Pgp axis.CONCLUSION SNHG5/miR-26b/Pgp regulates CRC chemosensitivity,providing potential therapeutic targets for the treatment of 5-Fu-resistant CRC.展开更多
The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understoo...The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understood.In this research,we examined the lncRNAs present in the dental epithelium(DE)and dental mesenchyme(DM)at the late bud,cap,and early bell stages of human fetal tooth development through bulk RNA sequencing.Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis.Specific lncRNAs expressed in the DE and DM,such as PANCR,MIR205HG,DLX6-AS1,and DNM3OS,were identified through a combination of bulk RNA sequencing and single-cell analysis.Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ,such as the inner enamel epithelium and coronal dental papilla(CDP).Functionally,we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells.These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.展开更多
The published article titled“Overexpression of long noncoding RNA PTENP1 inhibits cell proliferation and migration via suppression of miR-19b in breast cancer cells”has been retracted from Oncology Research,Vol.26,N...The published article titled“Overexpression of long noncoding RNA PTENP1 inhibits cell proliferation and migration via suppression of miR-19b in breast cancer cells”has been retracted from Oncology Research,Vol.26,No.6,2018,pp.869–878.展开更多
The published article titled“Overexpression of the Long Noncoding RNA FOXD2-AS1 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma Through the miR-195/Akt/mTOR Axis”has been retracted from Oncology ...The published article titled“Overexpression of the Long Noncoding RNA FOXD2-AS1 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma Through the miR-195/Akt/mTOR Axis”has been retracted from Oncology Research,Vol.28,No.1,2020,pp.65-73.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignant tumor with a poor prognosis,which is often associated with chronic hepatitis B virus infection in China.Our previous study has shown that long non-codin...BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignant tumor with a poor prognosis,which is often associated with chronic hepatitis B virus infection in China.Our previous study has shown that long non-coding RNA semaphorin 6Aantisense RNA 1(SEMA6A-AS1)was significantly downregulated in hepatitis B virus-related HCC and associated with poor prognosis.AIM To explore the underlying mechanism of SEMA6A-AS1 in HCC progression.METHODS The expression levels of SEMA6A-AS1 and SEMA6A were detected using quantitative polymerase chain reaction,immunohistochemistry and Western blot.A growth curve,colony formation,wound-healing and transwell(with or without Matrigel)assays were respectively performed to assess the proliferation,migration and invasion abilities of HCC cells.Cell cycle and apoptosis assays were performed by flow cytometry.To investigate the potential mechanism underpinning SEMA6A-AS1,we utilized tagged RNA affinity purification,dual luciferase reporter assay and immunofluorescence.RESULTS Downregulation of SEMA6A-AS1 in HCC was negatively correlated with SEMA6A protein expression.SEMA6A was upregulated in HCC and correlated with high alpha-fetoprotein level,high Edmondson-Steiner grade and poor prognosis.SEMA6A-AS1 significantly inhibited the proliferation,migration and invasion of HCC cells by combining with SEMA6A mRNA and promoting its degradation.SEMA6A protein promoted the proliferation,migration and invasion of HCC cells by regulating the actin cytoskeleton.CONCLUSION Our findings suggest that SEMA6A-AS1 can inhibit HCC progression through decreasing SEMA6A expression by promoting its mRNA degradation.SEMA6A-AS1 may be a prognostic biomarker and therapeutic target for HCC.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a malignancy found globally.Accumulating studies have shown that long noncoding RNAs(lncRNAs)play critical roles in HCC.However,the function of lncRNA in HCC remains poorly u...BACKGROUND Hepatocellular carcinoma(HCC)is a malignancy found globally.Accumulating studies have shown that long noncoding RNAs(lncRNAs)play critical roles in HCC.However,the function of lncRNA in HCC remains poorly understood.AIM To understand the effect of lncRNA W42 on HCC and dissect the underlying molecular mechanisms.METHODS We measured the expression of lncRNA W42 in HCC tissues and cells(Huh7 and SMMC-7721)by quantitative reverse transcriptase polymerase chain reaction.Receiver operating characteristic curves were used to assess the sensitivity and specificity of lncRNA W42 expression.HCC cells were transfected with pcDNA3.1-lncRNA W42 or shRNA-lncRNA W42.Cell functions were detected by cell counting Kit-8(CCK-8),colony formation,flow cytometry and Transwell assays.The interaction of lncRNA W42 and DBN1 was confirmed by RNA immunoprecipitation and RNA pull down assays.An HCC xenograft model was used to assess the role of lncRNA W42 on tumor growth in vivo.The Kaplan-Meier curve was used to evaluate the overall survival and recurrence-free survival after surgery in patients with HCC.RESULTS In this study,we identified a novel lncRNA(lncRNA W42),and investigated its biological functions and clinical significance in HCC.LncRNA W42 expression was upregulated in HCC tissues and cells.Overexpression of lncRNA W42 notably promoted the proliferative and invasion of HCC,and inhibited cell apoptosis.LncRNA W42 directly bound to DBN1 and activated the downstream pathway.LncRNA W42 knockdown suppressed HCC xenograft tumor growth in vivo.The clinical investigation revealed that HCC patients with high lncRNA W42 expression exhibited shorter survival times.CONCLUSION In vitro and in vivo results suggested that the novel lncRNA W42,which is upregulated in HCC,may serve as a potential candidate prognostic biomarker and therapeutic target in HCC patients.展开更多
Non-coding RNAs(ncRNAs)are a class of functional RNAs that play critical roles in different diseases.NcRNAs include microRNAs,long ncRNAs,and circular RNAs.They are highly expressed in the brain and are involved in th...Non-coding RNAs(ncRNAs)are a class of functional RNAs that play critical roles in different diseases.NcRNAs include microRNAs,long ncRNAs,and circular RNAs.They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes of central nervous system(CNS)diseases.Mounting evidence indicates that ncRNAs play key roles in CNS diseases.Further elucidating the mechanisms of ncRNA underlying the process of regulating glial function that may lead to the identification of novel therapeutic targets for CNS diseases.展开更多
Liver fibrosis is a wound-healing response following chronic liver injury caused by hepatitis virus infection,obesity,or excessive alcohol.It is a dynamic and reversible process characterized by the activation of hepa...Liver fibrosis is a wound-healing response following chronic liver injury caused by hepatitis virus infection,obesity,or excessive alcohol.It is a dynamic and reversible process characterized by the activation of hepatic stellate cells and excess accumulation of extracellular matrix.Advanced fibrosis could lead to cirrhosis and even liver cancer,which has become a significant health burden worldwide.Many studies have revealed that noncoding RNAs(ncRNAs),including microRNAs,long noncoding RNAs and circular RNAs,are involved in the pathogenesis and development of liver fibrosis by regulating signaling pathways including transforming growth factor-βpathway,phosphatidylinositol 3-kinase/protein kinase B pathway,and Wnt/β-catenin pathway.NcRNAs in serum or exosomes have been reported to tentatively applied in the diagnosis and staging of liver fibrosis and combined with elastography to improve the accuracy of diagnosis.NcRNAs mimics,ncRNAs in mesenchymal stem cell-derived exosomes,and lipid nanoparticles-encapsulated ncRNAs have become promising therapeutic approaches for the treatment of liver fibrosis.In this review,we update the latest knowledge on ncRNAs in the pathogenesis and progression of liver fibrosis,and discuss the potentials and challenges to use these ncRNAs for diagnosis,staging and treatment of liver fibrosis.All these will help us to develop a comprehensive understanding of the role of ncRNAs in liver fibrosis.展开更多
Embryonic stem cells (ESCs) hold great promises for treating and studying numerous devastating diseases. The molecular basis of their potential is not completely understood. Large noncoding RNAs (lncRNAs) are an i...Embryonic stem cells (ESCs) hold great promises for treating and studying numerous devastating diseases. The molecular basis of their potential is not completely understood. Large noncoding RNAs (lncRNAs) are an important class of gene regulators that play essential roles in a variety of physiologic and pathologic processes. Dozens of lncRNAs are now identified to control ESC self-renewal and differentiation. Research on lncRNAs may provide novel insights into manipulating the cell fate or reprogramming somatic cells into induced pluripotent stem cells (iPSCs). In this review, we summarize the recent research efforts in identifying functional lncRNAs and understanding how they act in ESCs, and discuss various future directions of this field.展开更多
AIM: To investigate the expression pattern of plasma long noncoding RNAs (lncRNAs) in Chrohn’s disease (CD) patients.METHODS: Microarray screening and qRT-PCR verification of lncRNAs and mRNAs were perform...AIM: To investigate the expression pattern of plasma long noncoding RNAs (lncRNAs) in Chrohn’s disease (CD) patients.METHODS: Microarray screening and qRT-PCR verification of lncRNAs and mRNAs were performed in CD and control subjects, followed by hierarchy clustering, GO and KEGG pathway analyses. Significantly dysregulated lncRNAs were categorized into subgroups of antisense lncRNAs, enhancer lncRNAs and lincRNAs. To predict the regulatory effect of lncRNAs on mRNAs, a CNC network analysis was performed and cross linked with significantly changed lncRNAs. The overlapping lncRNAs were randomly selected and verified by qRT-PCR in a larger cohort.RESULTS: Initially, there were 1211 up-regulated and 777 down-regulated lncRNAs as well as 1020 up-regulated and 953 down-regulated mRNAs after microarray analysis; a heat map based on these results showed good categorization into the CD and control groups. GUSBP2 and {'type':'entrez-nucleotide','attrs':{'text':'AF113016','term_id':'6642755','term_text':'AF113016'}}AF113016 had the highest fold change of the up- and down-regulated lncRNAs, whereas TBC1D17 and CCL3L3 had the highest fold change of the up- and down-regulated mRNAs. Six (SNX1, CYFIP2, CD6, CMTM8, STAT4 and IGFBP7) of 10 mRNAs and 8 ({'type':'entrez-nucleotide','attrs':{'text':'NR_033913','term_id':'299890801','term_text':'NR_033913'}}NR_033913, {'type':'entrez-nucleotide','attrs':{'text':'NR_038218','term_id':'333360887','term_text':'NR_038218'}}NR_038218, {'type':'entrez-nucleotide','attrs':{'text':'NR_036512','term_id':'302393555','term_text':'NR_036512'}}NR_036512, {'type':'entrez-nucleotide','attrs':{'text':'NR_049759','term_id':'388240827','term_text':'NR_049759'}}NR_049759, {'type':'entrez-nucleotide','attrs':{'text':'NR_033951','term_id':'300068996','term_text':'NR_033951'}}NR_033951, {'type':'entrez-nucleotide','attrs':{'text':'NR_045408','term_id':'354548835','term_text':'NR_045408'}}NR_045408, {'type':'entrez-nucleotide','attrs':{'text':'NR_038377','term_id':'335334999','term_text':'NR_038377'}}NR_038377 and {'type':'entrez-nucleotide','attrs':{'text':'NR_039976','term_id':'337756399','term_text':'NR_039976'}}NR_039976) of 14 lncRNAs showed the same change trends on the microarray and qRT-PCR results with statistical significance. Based on the qRT-PCR verified mRNAs, 1358 potential lncRNAs with 2697 positive correlations and 2287 negative correlations were predicted by the CNC network.CONCLUSION: The plasma lncRNAs profiles provide preliminary data for the non-invasive diagnosis of CD and a resource for further specific lncRNA-mRNA pathway exploration.展开更多
Given the rapid increase of patients with autoimmune diseases and the lack of satisfactory therapies,the discovery of novel and effective therapeutic targets have been in an urgent demand.Recent studies have revealed ...Given the rapid increase of patients with autoimmune diseases and the lack of satisfactory therapies,the discovery of novel and effective therapeutic targets have been in an urgent demand.Recent studies have revealed that long noncoding RNAs(lncRNAs)play crucial roles in the development of multiple sclerosis(MS),which provides a new opportunity of uncovering novel mechanism associated with the progression of MS.This review highlights the dysregulation of lncRNAs in the development of MS in patients and animal models.Additionally,the potential clinical relevance of lncRNAs severed as therapeutic targets and diagnostic markers are discussed.展开更多
BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long noncoding RNAs(lncRNAs)are active participators of diabetic nephropathy(DN).X inactive specific transcript(X...BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long noncoding RNAs(lncRNAs)are active participators of diabetic nephropathy(DN).X inactive specific transcript(XIST)expression has been reported to be elevated in the serum of DN patients.AIM To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell(RTEC)pyroptosis in DN.METHODS A DN rat model was established through streptozotocin injection,and XIST was knocked down by tail vein injection of the lentivirus LV sh-XIST.Renal metabolic and biochemical indices were detected,and pathological changes in the renal tissue were assessed.The expression of indicators related to inflammation and pyroptosis was also detected.High glucose(HG)was used to treat HK2 cells,and cell viability and lactate dehydrogenase(LDH)activity were detected after silencing XIST.The subcellular localization and downstream mechanism of XIST were investigated.Finally,a rescue experiment was carried out to verify that XIST regulates NLR family pyrin domain containing 3(NLRP3)/caspase-1-mediated RTEC pyroptosis through the microRNA-15-5p(miR-15b-5p)/Toll-like receptor 4(TLR4)axis.RESULTS XIST was highly expressed in the DN models.XIST silencing improved renal metabolism and biochemical indices and mitigated renal injury.The expression of inflammation and pyroptosis indicators was significantly increased in DN rats and HG-treated HK2 cells;cell viability was decreased and LDH activity was increased after HGtreatment. Silencing XIST inhibited RTEC pyroptosis by inhibiting NLRP3/caspase-1. Mechanistically,XIST sponged miR-15b-5p to regulate TLR4. Silencing XIST inhibited TLR4 by promotingmiR-15b-5p. miR-15b-5p inhibition or TLR4 overexpression averted the inhibitory effect ofsilencing XIST on HG-induced RTEC pyroptosis.CONCLUSIONSilencing XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury inDN by inhibiting NLRP3/caspase-1-mediated RTEC pyroptosis.展开更多
Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conven...Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conventional therapy and progresses to castration-resistant prostate cancer (CRPC), which is currently incurable. Thus, there is a critical need to identify biomarkers that will distinguish indolent from aggressive disease, as well as novel therapeutic targets for the prevention or treatment of CRPC. In recent years, long noncoding RNAs (IncRNAs) have emerged as an important class of biological molecules. LncRNAs are polyadenylated RNA species that share many similarities with protein-coding genes despite the fact that they are noncoding (not translated into proteins). They are usually transcribed by RNA polymerase II and exhibit the same epigenetic signatures as protein-coding genes. LncRNAs have also been implicated in the development and progression of variety of cancers, including prostate cancer. While a large number of IncRNAs exhibit tissue- and cancer-specific expression, their utility as diagnostic and prognostic biomarkers is just starting to be explored. In this review, we highlight recent findings on the functional role and molecular mechanisms of IncRNAs in the progression of prostate cancer and evaluate their use as potential biomarkers and therapeutic targets.展开更多
BACKGROUND Long noncoding RNA(lncRNA)ZNFX1-AS1(ZFAS1)is a newly discovered lncRNA,but its diagnostic value in gastric cancer is unclear.AIM To investigate the potential role of ZFAS1 in gastric cancer and to evaluate ...BACKGROUND Long noncoding RNA(lncRNA)ZNFX1-AS1(ZFAS1)is a newly discovered lncRNA,but its diagnostic value in gastric cancer is unclear.AIM To investigate the potential role of ZFAS1 in gastric cancer and to evaluate the clinical significance of ZFAS1 as a biomarker for gastric cancer screening.METHODS Quantitative real-time polymerase chain reaction(qRT-PCR)was used to screen for gastric cancer-associated lncRNAs in gastric cancer patients,gastric stromal tumor patients,gastritis or gastric ulcer patients,and healthy controls.Correlations between ZFAS1 expression and clinicopathological features were analyzed.The biological effects of ZFAS1 on the proliferation,migration,and invasion of gastric cancer cells were studied by MTT,colony formation,and transwell migration assays.The potential mechanism of ZFAS1 was demonstrated using enzyme-linked immunosorbent assay and qRT-PCR.The relationship between ZFAS1 and tumorigenesis was demonstrated using in vivo tumor formation assays.RESULTS The plasma level of lncRNA ZFAS1 was significantly higher in preoperative patients with gastric cancer than in individuals in the other 4 groups.Increased expression of ZFAS1 was significantly associated with lymph node metastasis,advanced TNM stage,and poor prognosis.ZFAS1 regulated the proliferation,migration,and invasion of gastric cancer cells and regulated the growth of gastric cancer cells in vivo.LIN28 and CAPRIN1 were identified as key downstream mediators of ZFAS1 in gastric cancer cells.CONCLUSION LncRNA ZFAS1 promoted the invasion and proliferation of gastric cancer cells by modulating LIN28 and CAPRIN1 expression,suggesting that ZFAS1 can be used as a potential diagnostic and prognostic biomarker in gastric cancer.展开更多
BACKGROUND Pancreatic ductal cancer(PDAC)has high malignancy and poor prognosis.Long noncoding RNAs(lncRNAs)are associated with high levels of malignancy,including PDAC.However,the biological and clinical significance...BACKGROUND Pancreatic ductal cancer(PDAC)has high malignancy and poor prognosis.Long noncoding RNAs(lncRNAs)are associated with high levels of malignancy,including PDAC.However,the biological and clinical significance of negative regulator of antiviral response(NRAV)in PDAC is unclear.AIM To study the regulatory role of lncRNA NRAV in PDAC.METHODS GEPIA analyzed lncRNA NRAV and miRNA(miR-299-3p)expression levels in PDAC tissues and measured them in PDAC cells by quantitative measurements in real time.The specific role of NRAV and miR-299-3p in cell proliferation and transfer potential was evaluated by cell formation analysis,Cell Counting Kit-8 and Transwell analysis.The relationship between NRAV and miR-299-3p was studied by predictive bioinformatics,RNA immunoassay,and fluorescence enzyme analysis.In vivo experiments included transplantation of simulated tumor cells under naked mice.RESULTS The expression level of lncRNA NRAV was higher in both tumor tissues and cell lines of PDAC and was negatively associated with the clinical survival of PDAC patients.Functionally,overexpression of NRAV promoted cell proliferation and metastasis of PDAC cells,while knockdown of NRAV reversed these effects.Finally,NRAV was performed as a molecular sponge of miR-299-3p.Moreover,overexpression of miR-299-3p could reverse the promoting effects of NRAV on cell proliferation and metastasis of PDAC cells.CONCLUSION NRAV facilitates progression of PDAC as a molecular sponge of miR-299-3p and may be a potential molecular marker for diagnosis and treatment of PDAC.展开更多
Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological pr...Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post-transcriptional levels. Here, we review the role of lnc RNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson’s disease(PD). These pathomechanisms include protein misfolding and aggregation, disordered protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, apoptosis, and neuroinflammation. This information will provide the basis of lnc RNA-based disease diagnosis and drug treatment for PD.展开更多
Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis,which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells(MSCs).Mounting evidence...Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis,which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells(MSCs).Mounting evidence indicates that a disturbance of bone homeostasis can trigger degenerative bone diseases,including osteoporosis and osteoarthritis.In addition to conventional genetic modifications,epigenetic modifications(i.e.,DNA methylation,histone modifications,and the expression of noncoding RNAs)are considered to be contributing factors that affect bone homeostasis.Long noncoding RNAs(lncRNAs)were previously regarded as‘transcriptional noise’with no biological functions.However,substantial evidence suggests that lncRNAs have roles in the epigenetic regulation of biological processes in MSCs and related diseases.In this review,we summarized the interactions between lncRNAs and epigenetic modifiers associated with osteo-/adipogenic differentiation of MSCs and the pathogenesis of degenerative bone diseases and highlighted promising lncRNA-based diagnostic and therapeutic targets for bone diseases.展开更多
Long noncoding RNAs(lncRNAs)participate in a variety of biological processes and diseases.However,the expression and function of lncRNAs after spinal cord injury has not been extensively analyzed.In this study of righ...Long noncoding RNAs(lncRNAs)participate in a variety of biological processes and diseases.However,the expression and function of lncRNAs after spinal cord injury has not been extensively analyzed.In this study of right side hemisection of the spinal cord at T10,we detected the expression of lncRNAs in the proximal tissue of T10 lamina at different time points and found 445 lncRNAs and 6522 mRNA were differentially expressed.We divided the differentially expressed lncRNAs into 26 expression trends and analyzed Profile 25 and Profile 2,the two expression trends with the most significant difference.Our results showed that the expression of 68 lncRNAs in Profile 25 rose first and remained high 3 days post-injury.There were 387 mRNAs co-expressed with the 68 lncRNAs in Profile 25.The co-expression network showed that the co-expressed genes were mainly enriched in cell division,inflammatory response,FcγR-mediated cell phagocytosis signaling pathway,cell cycle and apoptosis.The expression of 56 lncRNAs in Profile2 first declined and remained low after 3 days post-injury.There were 387 mRNAs co-expressed with the 56 lncRNAs in Profile 2.The co-expression network showed that the co-expressed genes were mainly enriched in the chemical synaptic transmission process and in the signaling pathway of neuroactive ligand-receptor interaction.The results provided the expression and regulatory network of the main lncRNAs after spinal cord injury and clarified their co-expressed gene enriched biological processes and signaling pathways.These findings provide a new direction for the clinical treatment of spinal cord injury.展开更多
文摘The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research,Vol.26,No.1,2018,pp.131–143.
文摘The published article titled“Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression inNon-Small Cell Lung Cancer”has been retracted fromOncology Research,Vol.25,No.6,2017,pp.1027–1037.DOI:10.3727/096504016X14822800040451 URL:https://www.techscience.com/or/v25n6/56885 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.
基金Supported by the National Natural Science Foundation of China,No.82404088China Postdoctoral Science Foundation,No.2023M730587Changshu Talent Scientific Project,No.KCH202304.
文摘BACKGROUND Colorectal cancer(CRC)is the second most prevalent cause of cancer-related mortality and is increasing in younger individuals.Chemotherapy,a crucial adjuvant systemic therapy for CRC management,often leads to resistance through poorly characterized underlying molecular mechanisms.The long noncoding RNA SNHG5 is highly expressed in CRC and promotes tumor proliferation and invasion,prompting us to hypothesize that SNHG5 may play a crucial role in the chemotherapeutic agent 5-fluorouracil(5-Fu)resistance in CRC.AIM To identify the function and mechanism of SNHG5 in 5-Fu resistance in CRC.METHODS Quantitative real-time polymerase chain reaction was performed to examine the expression of SNHG5 in CRC tissues from 225-Fu-sensitive patients and 145-Fu-resistant patients and in CRC cells and 5-Fu-resistant CRC cells.Cell viability and apoptosis were assessed in SNHG5-overexpressing CRC cells and SNHG5-knockdown 5-Furesistant CRC cells.SNHG5 function in 5-Fu resistance in CRC was further analyzed using a xenograft mouse model.SNHG5 interactions with microRNAs were predicted by bioinformatics analysis.Luciferase reporter and RNA immunoprecipitation assays were performed to verify the binding between SNHG5 and miR-26b.Rescue experiments were performed to validate the functional interaction between SNHG5 and the miR-26b/p-glycoprotein(Pgp)axis.RESULTS SNHG5 expression was upregulated in 5-Fu-resistant CRC tissues and 5-Fu-resistant CRC cells.In vitro functional experiments demonstrated that SNHG5 overexpression significantly reduced cell apoptosis and enhanced cell viability,whereas SNHG5 knockdown in 5-Fu-resistant CRC cells increased cell apoptosis and decreased cell viability upon 5-Fu treatment.In a xenograft mouse model,we confirmed that SNHG5 overexpression led to a reduction in 5-Fu sensitivity in CRC in vivo.Mechanistically,SNHG5 acted as a molecular sponge for miR-26b.Rescue experiments validated that SNHG5 conferred 5-Fu resistance in CRC by regulating the miR-26b/Pgp axis.CONCLUSION SNHG5/miR-26b/Pgp regulates CRC chemosensitivity,providing potential therapeutic targets for the treatment of 5-Fu-resistant CRC.
基金supported by the National Key Research and Development Program(2022YFA1104401)Beijing Municipal Government grant(Beijing Laboratory of Oral Health,PXM2021-014226-000041)+3 种基金Beijing Municipal Govemment(Beijing Scholar Program,PXM2021-014226-000020)National Natural Science Foundation of China(82030031,92149301,81991504,L2224038,82270945)Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202201)Chinese Research Unit of Tooth Development and Regeneration,Academy of Medical Sciences(2019-12M-5-031).
文摘The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understood.In this research,we examined the lncRNAs present in the dental epithelium(DE)and dental mesenchyme(DM)at the late bud,cap,and early bell stages of human fetal tooth development through bulk RNA sequencing.Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis.Specific lncRNAs expressed in the DE and DM,such as PANCR,MIR205HG,DLX6-AS1,and DNM3OS,were identified through a combination of bulk RNA sequencing and single-cell analysis.Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ,such as the inner enamel epithelium and coronal dental papilla(CDP).Functionally,we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells.These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
文摘The published article titled“Overexpression of long noncoding RNA PTENP1 inhibits cell proliferation and migration via suppression of miR-19b in breast cancer cells”has been retracted from Oncology Research,Vol.26,No.6,2018,pp.869–878.
文摘The published article titled“Overexpression of the Long Noncoding RNA FOXD2-AS1 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma Through the miR-195/Akt/mTOR Axis”has been retracted from Oncology Research,Vol.28,No.1,2020,pp.65-73.
基金Supported by Natural Science Foundation of Hunan Province,No.2021JJ41048 and No.S2019JJQNJJ2012and Changsha Natural Science Foundation,No.kq2208400.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignant tumor with a poor prognosis,which is often associated with chronic hepatitis B virus infection in China.Our previous study has shown that long non-coding RNA semaphorin 6Aantisense RNA 1(SEMA6A-AS1)was significantly downregulated in hepatitis B virus-related HCC and associated with poor prognosis.AIM To explore the underlying mechanism of SEMA6A-AS1 in HCC progression.METHODS The expression levels of SEMA6A-AS1 and SEMA6A were detected using quantitative polymerase chain reaction,immunohistochemistry and Western blot.A growth curve,colony formation,wound-healing and transwell(with or without Matrigel)assays were respectively performed to assess the proliferation,migration and invasion abilities of HCC cells.Cell cycle and apoptosis assays were performed by flow cytometry.To investigate the potential mechanism underpinning SEMA6A-AS1,we utilized tagged RNA affinity purification,dual luciferase reporter assay and immunofluorescence.RESULTS Downregulation of SEMA6A-AS1 in HCC was negatively correlated with SEMA6A protein expression.SEMA6A was upregulated in HCC and correlated with high alpha-fetoprotein level,high Edmondson-Steiner grade and poor prognosis.SEMA6A-AS1 significantly inhibited the proliferation,migration and invasion of HCC cells by combining with SEMA6A mRNA and promoting its degradation.SEMA6A protein promoted the proliferation,migration and invasion of HCC cells by regulating the actin cytoskeleton.CONCLUSION Our findings suggest that SEMA6A-AS1 can inhibit HCC progression through decreasing SEMA6A expression by promoting its mRNA degradation.SEMA6A-AS1 may be a prognostic biomarker and therapeutic target for HCC.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a malignancy found globally.Accumulating studies have shown that long noncoding RNAs(lncRNAs)play critical roles in HCC.However,the function of lncRNA in HCC remains poorly understood.AIM To understand the effect of lncRNA W42 on HCC and dissect the underlying molecular mechanisms.METHODS We measured the expression of lncRNA W42 in HCC tissues and cells(Huh7 and SMMC-7721)by quantitative reverse transcriptase polymerase chain reaction.Receiver operating characteristic curves were used to assess the sensitivity and specificity of lncRNA W42 expression.HCC cells were transfected with pcDNA3.1-lncRNA W42 or shRNA-lncRNA W42.Cell functions were detected by cell counting Kit-8(CCK-8),colony formation,flow cytometry and Transwell assays.The interaction of lncRNA W42 and DBN1 was confirmed by RNA immunoprecipitation and RNA pull down assays.An HCC xenograft model was used to assess the role of lncRNA W42 on tumor growth in vivo.The Kaplan-Meier curve was used to evaluate the overall survival and recurrence-free survival after surgery in patients with HCC.RESULTS In this study,we identified a novel lncRNA(lncRNA W42),and investigated its biological functions and clinical significance in HCC.LncRNA W42 expression was upregulated in HCC tissues and cells.Overexpression of lncRNA W42 notably promoted the proliferative and invasion of HCC,and inhibited cell apoptosis.LncRNA W42 directly bound to DBN1 and activated the downstream pathway.LncRNA W42 knockdown suppressed HCC xenograft tumor growth in vivo.The clinical investigation revealed that HCC patients with high lncRNA W42 expression exhibited shorter survival times.CONCLUSION In vitro and in vivo results suggested that the novel lncRNA W42,which is upregulated in HCC,may serve as a potential candidate prognostic biomarker and therapeutic target in HCC patients.
基金supported by grants from the Science and Technology innovation 2030-Major Project of the Ministry of Science and Technology of China(2021ZD0202904/2021ZD0202900)the National Science Fund Distinguished Young Scholars(82025033)+2 种基金the National Natural Science Foundation of China(82230115,82273914,81903591)ZhiShan Scholar Program of Southeast University(2242022R40059)the Jiangsu Provincial Key Laboratory of Critical Care Medicine(JSKLCCM-2022-02-008).
文摘Non-coding RNAs(ncRNAs)are a class of functional RNAs that play critical roles in different diseases.NcRNAs include microRNAs,long ncRNAs,and circular RNAs.They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes of central nervous system(CNS)diseases.Mounting evidence indicates that ncRNAs play key roles in CNS diseases.Further elucidating the mechanisms of ncRNA underlying the process of regulating glial function that may lead to the identification of novel therapeutic targets for CNS diseases.
基金Supported by Science and Technology Innovation Talent Project of Sichuan Province,No.2022JDRC0047the Central Government-directed Special Funds for Local Science and Technology Development Project,No.2021ZYD0085+1 种基金Natural Science Foundation of China,No.82102383Qin Chuangyuan Recruited High-level Innovation and Entrepreneurship Talents Project of Science and Technology Department of Shaanxi Province,No.QCYRCXM-2022-56.
文摘Liver fibrosis is a wound-healing response following chronic liver injury caused by hepatitis virus infection,obesity,or excessive alcohol.It is a dynamic and reversible process characterized by the activation of hepatic stellate cells and excess accumulation of extracellular matrix.Advanced fibrosis could lead to cirrhosis and even liver cancer,which has become a significant health burden worldwide.Many studies have revealed that noncoding RNAs(ncRNAs),including microRNAs,long noncoding RNAs and circular RNAs,are involved in the pathogenesis and development of liver fibrosis by regulating signaling pathways including transforming growth factor-βpathway,phosphatidylinositol 3-kinase/protein kinase B pathway,and Wnt/β-catenin pathway.NcRNAs in serum or exosomes have been reported to tentatively applied in the diagnosis and staging of liver fibrosis and combined with elastography to improve the accuracy of diagnosis.NcRNAs mimics,ncRNAs in mesenchymal stem cell-derived exosomes,and lipid nanoparticles-encapsulated ncRNAs have become promising therapeutic approaches for the treatment of liver fibrosis.In this review,we update the latest knowledge on ncRNAs in the pathogenesis and progression of liver fibrosis,and discuss the potentials and challenges to use these ncRNAs for diagnosis,staging and treatment of liver fibrosis.All these will help us to develop a comprehensive understanding of the role of ncRNAs in liver fibrosis.
基金supported by grants from Chinese Ministry of Science and Technology (Nos. 2011CBA01100 and 2012CB966700)the National Natural Science Foundation of China (No. 31221002)
文摘Embryonic stem cells (ESCs) hold great promises for treating and studying numerous devastating diseases. The molecular basis of their potential is not completely understood. Large noncoding RNAs (lncRNAs) are an important class of gene regulators that play essential roles in a variety of physiologic and pathologic processes. Dozens of lncRNAs are now identified to control ESC self-renewal and differentiation. Research on lncRNAs may provide novel insights into manipulating the cell fate or reprogramming somatic cells into induced pluripotent stem cells (iPSCs). In this review, we summarize the recent research efforts in identifying functional lncRNAs and understanding how they act in ESCs, and discuss various future directions of this field.
基金Supported by National Natural Science Foundation of China,No.81370008 and No.81000169Natural Science Foundation of Zhejiang Province,No.R2110159,No.LY15H030006 and No.LY16H030003Science Technology Project of Zhejiang Province,No.2014C33205
文摘AIM: To investigate the expression pattern of plasma long noncoding RNAs (lncRNAs) in Chrohn’s disease (CD) patients.METHODS: Microarray screening and qRT-PCR verification of lncRNAs and mRNAs were performed in CD and control subjects, followed by hierarchy clustering, GO and KEGG pathway analyses. Significantly dysregulated lncRNAs were categorized into subgroups of antisense lncRNAs, enhancer lncRNAs and lincRNAs. To predict the regulatory effect of lncRNAs on mRNAs, a CNC network analysis was performed and cross linked with significantly changed lncRNAs. The overlapping lncRNAs were randomly selected and verified by qRT-PCR in a larger cohort.RESULTS: Initially, there were 1211 up-regulated and 777 down-regulated lncRNAs as well as 1020 up-regulated and 953 down-regulated mRNAs after microarray analysis; a heat map based on these results showed good categorization into the CD and control groups. GUSBP2 and {'type':'entrez-nucleotide','attrs':{'text':'AF113016','term_id':'6642755','term_text':'AF113016'}}AF113016 had the highest fold change of the up- and down-regulated lncRNAs, whereas TBC1D17 and CCL3L3 had the highest fold change of the up- and down-regulated mRNAs. Six (SNX1, CYFIP2, CD6, CMTM8, STAT4 and IGFBP7) of 10 mRNAs and 8 ({'type':'entrez-nucleotide','attrs':{'text':'NR_033913','term_id':'299890801','term_text':'NR_033913'}}NR_033913, {'type':'entrez-nucleotide','attrs':{'text':'NR_038218','term_id':'333360887','term_text':'NR_038218'}}NR_038218, {'type':'entrez-nucleotide','attrs':{'text':'NR_036512','term_id':'302393555','term_text':'NR_036512'}}NR_036512, {'type':'entrez-nucleotide','attrs':{'text':'NR_049759','term_id':'388240827','term_text':'NR_049759'}}NR_049759, {'type':'entrez-nucleotide','attrs':{'text':'NR_033951','term_id':'300068996','term_text':'NR_033951'}}NR_033951, {'type':'entrez-nucleotide','attrs':{'text':'NR_045408','term_id':'354548835','term_text':'NR_045408'}}NR_045408, {'type':'entrez-nucleotide','attrs':{'text':'NR_038377','term_id':'335334999','term_text':'NR_038377'}}NR_038377 and {'type':'entrez-nucleotide','attrs':{'text':'NR_039976','term_id':'337756399','term_text':'NR_039976'}}NR_039976) of 14 lncRNAs showed the same change trends on the microarray and qRT-PCR results with statistical significance. Based on the qRT-PCR verified mRNAs, 1358 potential lncRNAs with 2697 positive correlations and 2287 negative correlations were predicted by the CNC network.CONCLUSION: The plasma lncRNAs profiles provide preliminary data for the non-invasive diagnosis of CD and a resource for further specific lncRNA-mRNA pathway exploration.
基金supported by the National Natural Science Foundation of China(Nos.81573444,81603647 and81973221)the Natural Science Foundation of Jiangsu Province of China(No.BK20171391)+2 种基金the Special Foundation of Rheumatoid Arthritis(No.Z-2018-40)the Innovation Team of the “Double-First Class” Disciplines(No.CPU2018GF08)the Medical Science and Technology Development Foundation of Nanjing Medical University(No.2017NJMUZD055)
文摘Given the rapid increase of patients with autoimmune diseases and the lack of satisfactory therapies,the discovery of novel and effective therapeutic targets have been in an urgent demand.Recent studies have revealed that long noncoding RNAs(lncRNAs)play crucial roles in the development of multiple sclerosis(MS),which provides a new opportunity of uncovering novel mechanism associated with the progression of MS.This review highlights the dysregulation of lncRNAs in the development of MS in patients and animal models.Additionally,the potential clinical relevance of lncRNAs severed as therapeutic targets and diagnostic markers are discussed.
基金Supported by Natural Science Foundation of Shenzhen University General Hospital (SUGH2020QD011)
文摘BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long noncoding RNAs(lncRNAs)are active participators of diabetic nephropathy(DN).X inactive specific transcript(XIST)expression has been reported to be elevated in the serum of DN patients.AIM To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell(RTEC)pyroptosis in DN.METHODS A DN rat model was established through streptozotocin injection,and XIST was knocked down by tail vein injection of the lentivirus LV sh-XIST.Renal metabolic and biochemical indices were detected,and pathological changes in the renal tissue were assessed.The expression of indicators related to inflammation and pyroptosis was also detected.High glucose(HG)was used to treat HK2 cells,and cell viability and lactate dehydrogenase(LDH)activity were detected after silencing XIST.The subcellular localization and downstream mechanism of XIST were investigated.Finally,a rescue experiment was carried out to verify that XIST regulates NLR family pyrin domain containing 3(NLRP3)/caspase-1-mediated RTEC pyroptosis through the microRNA-15-5p(miR-15b-5p)/Toll-like receptor 4(TLR4)axis.RESULTS XIST was highly expressed in the DN models.XIST silencing improved renal metabolism and biochemical indices and mitigated renal injury.The expression of inflammation and pyroptosis indicators was significantly increased in DN rats and HG-treated HK2 cells;cell viability was decreased and LDH activity was increased after HGtreatment. Silencing XIST inhibited RTEC pyroptosis by inhibiting NLRP3/caspase-1. Mechanistically,XIST sponged miR-15b-5p to regulate TLR4. Silencing XIST inhibited TLR4 by promotingmiR-15b-5p. miR-15b-5p inhibition or TLR4 overexpression averted the inhibitory effect ofsilencing XIST on HG-induced RTEC pyroptosis.CONCLUSIONSilencing XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury inDN by inhibiting NLRP3/caspase-1-mediated RTEC pyroptosis.
文摘Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conventional therapy and progresses to castration-resistant prostate cancer (CRPC), which is currently incurable. Thus, there is a critical need to identify biomarkers that will distinguish indolent from aggressive disease, as well as novel therapeutic targets for the prevention or treatment of CRPC. In recent years, long noncoding RNAs (IncRNAs) have emerged as an important class of biological molecules. LncRNAs are polyadenylated RNA species that share many similarities with protein-coding genes despite the fact that they are noncoding (not translated into proteins). They are usually transcribed by RNA polymerase II and exhibit the same epigenetic signatures as protein-coding genes. LncRNAs have also been implicated in the development and progression of variety of cancers, including prostate cancer. While a large number of IncRNAs exhibit tissue- and cancer-specific expression, their utility as diagnostic and prognostic biomarkers is just starting to be explored. In this review, we highlight recent findings on the functional role and molecular mechanisms of IncRNAs in the progression of prostate cancer and evaluate their use as potential biomarkers and therapeutic targets.
基金Supported by Beijing Natural Science Foundation,No.7172225
文摘BACKGROUND Long noncoding RNA(lncRNA)ZNFX1-AS1(ZFAS1)is a newly discovered lncRNA,but its diagnostic value in gastric cancer is unclear.AIM To investigate the potential role of ZFAS1 in gastric cancer and to evaluate the clinical significance of ZFAS1 as a biomarker for gastric cancer screening.METHODS Quantitative real-time polymerase chain reaction(qRT-PCR)was used to screen for gastric cancer-associated lncRNAs in gastric cancer patients,gastric stromal tumor patients,gastritis or gastric ulcer patients,and healthy controls.Correlations between ZFAS1 expression and clinicopathological features were analyzed.The biological effects of ZFAS1 on the proliferation,migration,and invasion of gastric cancer cells were studied by MTT,colony formation,and transwell migration assays.The potential mechanism of ZFAS1 was demonstrated using enzyme-linked immunosorbent assay and qRT-PCR.The relationship between ZFAS1 and tumorigenesis was demonstrated using in vivo tumor formation assays.RESULTS The plasma level of lncRNA ZFAS1 was significantly higher in preoperative patients with gastric cancer than in individuals in the other 4 groups.Increased expression of ZFAS1 was significantly associated with lymph node metastasis,advanced TNM stage,and poor prognosis.ZFAS1 regulated the proliferation,migration,and invasion of gastric cancer cells and regulated the growth of gastric cancer cells in vivo.LIN28 and CAPRIN1 were identified as key downstream mediators of ZFAS1 in gastric cancer cells.CONCLUSION LncRNA ZFAS1 promoted the invasion and proliferation of gastric cancer cells by modulating LIN28 and CAPRIN1 expression,suggesting that ZFAS1 can be used as a potential diagnostic and prognostic biomarker in gastric cancer.
基金Supported by the National Natural Science Foundation of China,No.81974372
文摘BACKGROUND Pancreatic ductal cancer(PDAC)has high malignancy and poor prognosis.Long noncoding RNAs(lncRNAs)are associated with high levels of malignancy,including PDAC.However,the biological and clinical significance of negative regulator of antiviral response(NRAV)in PDAC is unclear.AIM To study the regulatory role of lncRNA NRAV in PDAC.METHODS GEPIA analyzed lncRNA NRAV and miRNA(miR-299-3p)expression levels in PDAC tissues and measured them in PDAC cells by quantitative measurements in real time.The specific role of NRAV and miR-299-3p in cell proliferation and transfer potential was evaluated by cell formation analysis,Cell Counting Kit-8 and Transwell analysis.The relationship between NRAV and miR-299-3p was studied by predictive bioinformatics,RNA immunoassay,and fluorescence enzyme analysis.In vivo experiments included transplantation of simulated tumor cells under naked mice.RESULTS The expression level of lncRNA NRAV was higher in both tumor tissues and cell lines of PDAC and was negatively associated with the clinical survival of PDAC patients.Functionally,overexpression of NRAV promoted cell proliferation and metastasis of PDAC cells,while knockdown of NRAV reversed these effects.Finally,NRAV was performed as a molecular sponge of miR-299-3p.Moreover,overexpression of miR-299-3p could reverse the promoting effects of NRAV on cell proliferation and metastasis of PDAC cells.CONCLUSION NRAV facilitates progression of PDAC as a molecular sponge of miR-299-3p and may be a potential molecular marker for diagnosis and treatment of PDAC.
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2017-I2M-2-005 and 2016-I2M-2-006Beijing Natural Science Foundation,Grant/Award Number:5171001
文摘Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post-transcriptional levels. Here, we review the role of lnc RNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson’s disease(PD). These pathomechanisms include protein misfolding and aggregation, disordered protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, apoptosis, and neuroinflammation. This information will provide the basis of lnc RNA-based disease diagnosis and drug treatment for PD.
基金the National Natural Science Foundation of China,No.81870743 and No.81771048.
文摘Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis,which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells(MSCs).Mounting evidence indicates that a disturbance of bone homeostasis can trigger degenerative bone diseases,including osteoporosis and osteoarthritis.In addition to conventional genetic modifications,epigenetic modifications(i.e.,DNA methylation,histone modifications,and the expression of noncoding RNAs)are considered to be contributing factors that affect bone homeostasis.Long noncoding RNAs(lncRNAs)were previously regarded as‘transcriptional noise’with no biological functions.However,substantial evidence suggests that lncRNAs have roles in the epigenetic regulation of biological processes in MSCs and related diseases.In this review,we summarized the interactions between lncRNAs and epigenetic modifiers associated with osteo-/adipogenic differentiation of MSCs and the pathogenesis of degenerative bone diseases and highlighted promising lncRNA-based diagnostic and therapeutic targets for bone diseases.
文摘Long noncoding RNAs(lncRNAs)participate in a variety of biological processes and diseases.However,the expression and function of lncRNAs after spinal cord injury has not been extensively analyzed.In this study of right side hemisection of the spinal cord at T10,we detected the expression of lncRNAs in the proximal tissue of T10 lamina at different time points and found 445 lncRNAs and 6522 mRNA were differentially expressed.We divided the differentially expressed lncRNAs into 26 expression trends and analyzed Profile 25 and Profile 2,the two expression trends with the most significant difference.Our results showed that the expression of 68 lncRNAs in Profile 25 rose first and remained high 3 days post-injury.There were 387 mRNAs co-expressed with the 68 lncRNAs in Profile 25.The co-expression network showed that the co-expressed genes were mainly enriched in cell division,inflammatory response,FcγR-mediated cell phagocytosis signaling pathway,cell cycle and apoptosis.The expression of 56 lncRNAs in Profile2 first declined and remained low after 3 days post-injury.There were 387 mRNAs co-expressed with the 56 lncRNAs in Profile 2.The co-expression network showed that the co-expressed genes were mainly enriched in the chemical synaptic transmission process and in the signaling pathway of neuroactive ligand-receptor interaction.The results provided the expression and regulatory network of the main lncRNAs after spinal cord injury and clarified their co-expressed gene enriched biological processes and signaling pathways.These findings provide a new direction for the clinical treatment of spinal cord injury.