microRNAs （miRNAs） are a class of endogenous, single-stranded non-coding RNAs of 20- 23 nucleotides in length, functioning as negative regulators of gene expression at the post-transcriptional level. The dysregulati...microRNAs （miRNAs） are a class of endogenous, single-stranded non-coding RNAs of 20- 23 nucleotides in length, functioning as negative regulators of gene expression at the post-transcriptional level. The dysregulation of miRNAs has been demonstrated to play critical roles in tumorigenesis, either through inhibiting tumor suppressor genes or activating oncogenes inappropriately. Besides their promising clinical applications in cancer diagnosis and treatment, recent studies have uncovered that miRNAs could act as a regulatory language, through which messenger RNAs, transcribed pseudogenes, and long noncoding RNAs crosstalk with each other and form a novel regulatory network. RNA transcripts involved in this network have been termed as competing endogenous RNAs （ceRNAs）, since they influence each other＇s level by competing for the same pool of miRNAs through miRNA response elements （MREs） on their target transcripts. The discovery of miRNA-ceRNA network not only provides the possibility of an additional level of post-transcriptional regulation, but also dictates a reassessment of the existing regulatory pathways involved in cancer initiation and progression.展开更多
Competing endogenous RNAs(ceRNAs)are transcripts that possess highly similar microRNA response elements(MREs).microRNAs(miRNAs)are short,endogenous,single-stranded non-coding RNAs(ncRNAs)that can repress gene expressi...Competing endogenous RNAs(ceRNAs)are transcripts that possess highly similar microRNA response elements(MREs).microRNAs(miRNAs)are short,endogenous,single-stranded non-coding RNAs(ncRNAs)that can repress gene expression by binding to MREs on the 3’untranslated regions(UTRs)of the target mRNA transcripts to suppress gene expression by promoting mRNA degradation and/or inhibiting protein translation.mRNA transcripts,circular RNAs(circRNAs),long non-coding RNAs(lncRNAs),and transcribed pseudogenes could share similar MREs,and they can compete for the same pool of miRNAs.These ceRNAs may affect the level of one another by competing for their shared miRNAs.This interplay between different RNAs constitutes a ceRNA network,which regulates many important biological processes.Cancer drug resistance is a major factor leading to treatment failure in patients receiving chemotherapy.It can be acquired through genetic,epigenetic,and various tumor microenvironment mechanisms.The involvement of ceRNA crosstalk and its disruption in chemotherapy resistance is attracting attention in the cancer research community.This review presents an updated summary of the latest research on ceRNA dysregulation causing drug resistance across different cancer types and chemotherapeutic drug classes.Interestingly,accumulating evidence suggests that ceRNAs may be used as prognostic biomarkers to predict clinical response to cancer chemotherapy.Nevertheless,detailed experimental investigations of the putative ceRNA networks generated by computational algorithms are needed to support their translation for therapeutic and prognostic applications.展开更多
BACKGROUND Colonic neuroendocrine carcinomas(NECs)are highly malignant and invasive with poor prognosis.Long noncoding RNAs(LncRNAs)participate in the tumorigenesis and metastasis of multiple cancers AIM To detect the...BACKGROUND Colonic neuroendocrine carcinomas(NECs)are highly malignant and invasive with poor prognosis.Long noncoding RNAs(LncRNAs)participate in the tumorigenesis and metastasis of multiple cancers AIM To detect the roles and mechanisms of lncRNA prostate cancer associated transcript 6(PCAT6)in the progression of colonic NEC.METHODS Human NEC and adjacent normal samples were collected for immunohistochemistry staining of CgA and real-time quantitative polymerase chain reaction(RT-qPCR)of PCAT6 mRNA level.Subcutaneous xenograft tumor model and lung metastasis model were established in nude mice.The lung tissues were stained by hematoxylin and eosin to assess pulmonary metastasis.The expression of epithelial-mesenchymal transition(EMT)-related markers and pathway-related genes was measured by RT-qPCR and western blotting.CD56 expression was assessed by immunofluorescence staining.The biological functions of PCAT6 were examined by cell counting kit-8,colony formation assays,Transwell assays and wound healing assays.The interaction between PCAT6 and its potential downstream target was verified by luciferase reporter assays.RESULTS LncRNA PCAT6 was upregulated in human NEC samples and LCC-18 cells,and its high expression was positively correlated with poor prognosis in patients with colonic NEC.Additionally,the expression of PCAT6 was positively associated with the proliferation,migration,invasion,and EMT of LCC-18 cells.Moreover,PCAT6 facilitated tumor growth,lung metastasis and EMT in xenografts.Mechanistically,PCAT6 promoted the activation of MAPK to enhance the EMT in colonic NEC by targeting miR-326.CONCLUSION In conclusion,lncRNA PCAT6 accelerates the process of colonic NEC by activating ERK/p38 MAPK signaling through targeting miR-326.These results might provide useful information for exploring the potential therapeutic targets in colonic NEC.展开更多
目的:寻找影响胃癌发生发展的衰老基因,构建内源竞争性RNA (ceRNA)调控网络,为发掘胃癌有效的诊断、预后生物标志物和治疗靶点提供依据。方法:从癌症基因组图谱(TCGA)数据库下载胃癌的表达数据和临床生存数据,在Aging Atlas数据库中获...目的:寻找影响胃癌发生发展的衰老基因,构建内源竞争性RNA (ceRNA)调控网络,为发掘胃癌有效的诊断、预后生物标志物和治疗靶点提供依据。方法:从癌症基因组图谱(TCGA)数据库下载胃癌的表达数据和临床生存数据,在Aging Atlas数据库中获取衰老基因,使用R软件中“DESeq2”程序包进行差异分析并采用Cox回归及Kaplan-Meier生存分析的方法筛选在胃癌中表达差异且与预后相关的衰老基因。通过Starbase数据库筛选具有靶向关系的miRNAs和lncRNAs,分别进行相关性分析和生存分析用于构建ceRNA调控网络。结果:对502个衰老基因分析显示SERPINE1基因在胃癌组织中显著高表达,且其高表达时患者预后较差。之后以SERPINE1作为关键基因构建一个与胃癌患者预后相关的ceRNA网络,其包含1个mRNA、1个miRNA和1个lncRNA,并以此基因构建胃癌的预后风险模型,最后进行通路、功能及免疫相关性分析。结论:本研究对衰老基因的分析及ceRNA网络的构建有助于进一步探索胃癌发生发展的分子机制,对发现预后标志物和治疗靶点至关重要。Objective: Searching for aging genes affecting the occurrence and development of gastric cancer and constructing competitive endogenous RNA (ceRNA) regulatory networks provide evidence for exploring effective diagnostic and prognostic biomarkers and therapeutic targets of gastric cancer. Methods: Expression data and clinical survival data of gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) database. Senescence-related genes were obtained from the Aging Atlas database. Differential analysis was performed using the “DESeq2” package in R software. Cox regression and Kaplan-Meier survival analysis methods were employed to screen for senescence-related genes that are differentially expressed in gastric cancer and associated with prognosis. The Starbase database was used to identify miRNAs and lncRNAs with target relationships. Correlation analysis and survival analysis were conducted to construct the ceRNA regulatory network. Results: The analysis of 502 aging genes showed that the SERPINE1 gene was highly expressed in gastric cancer tissues, and the prognosis of patients was poor when it was highly expressed. Then SERPINE1 was used as the key gene to construct a ceRNA network correlated with survival in gastric cancer patients, which included one mRNA, one miRNA, and one lncRNA. The prognostic risk model of gastric cancer was constructed with the SERPINE1 gene. Finally, the pathway, functional enrichment analysis, and immune correlation analysis were carried out. Conclusion: The analysis of aging genes and the construction of the ceRNA network in this study are helpful to further explore the molecular mechanism of the occurrence and development of gastric cancer, which is crucial for the discovery of the prognostic markers and therapeutic targets.展开更多
基金supported by the grants from the National Natural Science Foundation of China (No. 81272766)Capital Medical Development and Research Foundation (No. 2009-2093)+2 种基金Clinical Characteristics and Application Research of Capital (No. Z121107001012130)Beijing Natural Science Foundation (No. 7132054)New Star of Science and Technology Program of Beijing (No. 2011060)
文摘microRNAs （miRNAs） are a class of endogenous, single-stranded non-coding RNAs of 20- 23 nucleotides in length, functioning as negative regulators of gene expression at the post-transcriptional level. The dysregulation of miRNAs has been demonstrated to play critical roles in tumorigenesis, either through inhibiting tumor suppressor genes or activating oncogenes inappropriately. Besides their promising clinical applications in cancer diagnosis and treatment, recent studies have uncovered that miRNAs could act as a regulatory language, through which messenger RNAs, transcribed pseudogenes, and long noncoding RNAs crosstalk with each other and form a novel regulatory network. RNA transcripts involved in this network have been termed as competing endogenous RNAs （ceRNAs）, since they influence each other＇s level by competing for the same pool of miRNAs through miRNA response elements （MREs） on their target transcripts. The discovery of miRNA-ceRNA network not only provides the possibility of an additional level of post-transcriptional regulation, but also dictates a reassessment of the existing regulatory pathways involved in cancer initiation and progression.
基金support provided by the Chinese University of Hong Kong(Direct Grant 4054782)Guangdong-Hong Kong-Macao New Drug Screening Joint Laboratory(Project 8326200)the SKL Open Fund(SKLOF-X)from the Institute of Chinese Medicine(CUHK).
文摘Competing endogenous RNAs(ceRNAs)are transcripts that possess highly similar microRNA response elements(MREs).microRNAs(miRNAs)are short,endogenous,single-stranded non-coding RNAs(ncRNAs)that can repress gene expression by binding to MREs on the 3’untranslated regions(UTRs)of the target mRNA transcripts to suppress gene expression by promoting mRNA degradation and/or inhibiting protein translation.mRNA transcripts,circular RNAs(circRNAs),long non-coding RNAs(lncRNAs),and transcribed pseudogenes could share similar MREs,and they can compete for the same pool of miRNAs.These ceRNAs may affect the level of one another by competing for their shared miRNAs.This interplay between different RNAs constitutes a ceRNA network,which regulates many important biological processes.Cancer drug resistance is a major factor leading to treatment failure in patients receiving chemotherapy.It can be acquired through genetic,epigenetic,and various tumor microenvironment mechanisms.The involvement of ceRNA crosstalk and its disruption in chemotherapy resistance is attracting attention in the cancer research community.This review presents an updated summary of the latest research on ceRNA dysregulation causing drug resistance across different cancer types and chemotherapeutic drug classes.Interestingly,accumulating evidence suggests that ceRNAs may be used as prognostic biomarkers to predict clinical response to cancer chemotherapy.Nevertheless,detailed experimental investigations of the putative ceRNA networks generated by computational algorithms are needed to support their translation for therapeutic and prognostic applications.
文摘BACKGROUND Colonic neuroendocrine carcinomas(NECs)are highly malignant and invasive with poor prognosis.Long noncoding RNAs(LncRNAs)participate in the tumorigenesis and metastasis of multiple cancers AIM To detect the roles and mechanisms of lncRNA prostate cancer associated transcript 6(PCAT6)in the progression of colonic NEC.METHODS Human NEC and adjacent normal samples were collected for immunohistochemistry staining of CgA and real-time quantitative polymerase chain reaction(RT-qPCR)of PCAT6 mRNA level.Subcutaneous xenograft tumor model and lung metastasis model were established in nude mice.The lung tissues were stained by hematoxylin and eosin to assess pulmonary metastasis.The expression of epithelial-mesenchymal transition(EMT)-related markers and pathway-related genes was measured by RT-qPCR and western blotting.CD56 expression was assessed by immunofluorescence staining.The biological functions of PCAT6 were examined by cell counting kit-8,colony formation assays,Transwell assays and wound healing assays.The interaction between PCAT6 and its potential downstream target was verified by luciferase reporter assays.RESULTS LncRNA PCAT6 was upregulated in human NEC samples and LCC-18 cells,and its high expression was positively correlated with poor prognosis in patients with colonic NEC.Additionally,the expression of PCAT6 was positively associated with the proliferation,migration,invasion,and EMT of LCC-18 cells.Moreover,PCAT6 facilitated tumor growth,lung metastasis and EMT in xenografts.Mechanistically,PCAT6 promoted the activation of MAPK to enhance the EMT in colonic NEC by targeting miR-326.CONCLUSION In conclusion,lncRNA PCAT6 accelerates the process of colonic NEC by activating ERK/p38 MAPK signaling through targeting miR-326.These results might provide useful information for exploring the potential therapeutic targets in colonic NEC.
文摘目的:寻找影响胃癌发生发展的衰老基因,构建内源竞争性RNA (ceRNA)调控网络,为发掘胃癌有效的诊断、预后生物标志物和治疗靶点提供依据。方法:从癌症基因组图谱(TCGA)数据库下载胃癌的表达数据和临床生存数据,在Aging Atlas数据库中获取衰老基因,使用R软件中“DESeq2”程序包进行差异分析并采用Cox回归及Kaplan-Meier生存分析的方法筛选在胃癌中表达差异且与预后相关的衰老基因。通过Starbase数据库筛选具有靶向关系的miRNAs和lncRNAs,分别进行相关性分析和生存分析用于构建ceRNA调控网络。结果:对502个衰老基因分析显示SERPINE1基因在胃癌组织中显著高表达,且其高表达时患者预后较差。之后以SERPINE1作为关键基因构建一个与胃癌患者预后相关的ceRNA网络,其包含1个mRNA、1个miRNA和1个lncRNA,并以此基因构建胃癌的预后风险模型,最后进行通路、功能及免疫相关性分析。结论:本研究对衰老基因的分析及ceRNA网络的构建有助于进一步探索胃癌发生发展的分子机制,对发现预后标志物和治疗靶点至关重要。Objective: Searching for aging genes affecting the occurrence and development of gastric cancer and constructing competitive endogenous RNA (ceRNA) regulatory networks provide evidence for exploring effective diagnostic and prognostic biomarkers and therapeutic targets of gastric cancer. Methods: Expression data and clinical survival data of gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) database. Senescence-related genes were obtained from the Aging Atlas database. Differential analysis was performed using the “DESeq2” package in R software. Cox regression and Kaplan-Meier survival analysis methods were employed to screen for senescence-related genes that are differentially expressed in gastric cancer and associated with prognosis. The Starbase database was used to identify miRNAs and lncRNAs with target relationships. Correlation analysis and survival analysis were conducted to construct the ceRNA regulatory network. Results: The analysis of 502 aging genes showed that the SERPINE1 gene was highly expressed in gastric cancer tissues, and the prognosis of patients was poor when it was highly expressed. Then SERPINE1 was used as the key gene to construct a ceRNA network correlated with survival in gastric cancer patients, which included one mRNA, one miRNA, and one lncRNA. The prognostic risk model of gastric cancer was constructed with the SERPINE1 gene. Finally, the pathway, functional enrichment analysis, and immune correlation analysis were carried out. Conclusion: The analysis of aging genes and the construction of the ceRNA network in this study are helpful to further explore the molecular mechanism of the occurrence and development of gastric cancer, which is crucial for the discovery of the prognostic markers and therapeutic targets.
