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
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.
