Upregulation of Cyclin B1 by miRNA and its implications in cancer
Vera Huang,Robert F. Place,Victoria Portnoy,Ji Wang,Zhongxia Qi,Zhe-Jun Jia,Angela J. Yu,Marc A. Shuman,Jingwei Yu,Long-Cheng Li +9 more
Reads0
Chats0
TLDR
The findings reveal an endogenous system by which miRNA functions to activate Ccnb1 expression in mouse cells and manipulate in vivo tumor development/growth.Abstract:
It is largely recognized that microRNAs (miRNAs) function to silence gene expression by targeting 3'UTR regions. However, miRNAs have also been implicated to positively-regulate gene expression by targeting promoter elements, a phenomenon known as RNA activation (RNAa). In the present study, we show that expression of mouse Cyclin B1 (Ccnb1) is dependent on key factors involved in miRNA biogenesis and function (i.e. Dicer, Drosha, Ago1 and Ago2). In silico analysis identifies highly-complementary sites for 21 miRNAs in the Ccnb1 promoter. Experimental validation identified three miRNAs (miR-744, miR-1186 and miR-466d-3p) that induce Ccnb1 expression in mouse cell lines. Conversely, knockdown of endogenous miR-744 led to decreased Ccnb1 levels. Chromatin immunoprecipitation (ChIP) analysis revealed that Ago1 was selectively associated with the Ccnb1 promoter and miR-744 increased enrichment of RNA polymerase II (RNAP II) and trimethylation of histone 3 at lysine 4 (H3K4me3) at the Ccnb1 transcription start site. Functionally, short-term overexpression of miR-744 and miR-1186 resulted in enhanced cell proliferation, while prolonged expression caused chromosomal instability and in vivo tumor suppression. Such phenotypes were recapitulated by overexpression of Ccnb1. Our findings reveal an endogenous system by which miRNA functions to activate Ccnb1 expression in mouse cells and manipulate in vivo tumor development/growth.read more
Citations
More filters
Journal ArticleDOI
MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions.
TL;DR: The finding that small non-coding RNAs (ncRNAs) are able to control gene expression in a sequence specific manner has had a massive impact on biology and it is becoming evident that miRNAs also have specific nuclear functions.
Journal ArticleDOI
DIANA-TarBase v7.0: indexing more than half a million experimentally supported miRNA:mRNA interactions
Ioannis S. Vlachos,Ioannis S. Vlachos,Maria D. Paraskevopoulou,Dimitra Karagkouni,Georgios Georgakilas,Thanasis Vergoulis,Ilias Kanellos,Ioannis-Laertis Anastasopoulos,Sofia Maniou,Konstantina Karathanou,Despoina Kalfakakou,Athanasios Fevgas,Theodore Dalamagas,Artemis G. Hatzigeorgiou +13 more
TL;DR: DIANA-TarBase v7.0 aims to provide for the first time hundreds of thousands of high-quality manually curated experimentally validated miRNA:gene interactions, enhanced with detailed meta-data, which enables users to easily identify positive or negative experimental results, the utilized experimental methodology, experimental conditions including cell/tissue type and treatment.
Journal ArticleDOI
Regulatory network of miRNA on its target: coordination between transcriptional and post-transcriptional regulation of gene expression
TL;DR: In this article, a review of the mechanisms of miRNA-mediated gene transcriptional and post-transcriptional regulation are summarized, and the synergistic effects among these actions which form a regulatory network of a miRNA on its target are particularly elaborated.
Journal ArticleDOI
Nuclear functions of mammalian MicroRNAs in gene regulation, immunity and cancer
TL;DR: The nuclear functions of miRNA in immunity, tumorigenesis and invasiveness of tumor is explored, and active regulatory functions of nuclear miRNAs were found including PTGS, transcriptional gene silencing (TGS), and transcriptional genes activation (TGA), in which miRN as bind nascent RNA transcripts, gene promoter regions or enhancer regions and exert further effects via epigenetic pathways.
Journal ArticleDOI
MicroRNAs Activate Gene Transcription Epigenetically as an Enhancer Trigger
Min Xiao,Jin Li,Wei Li,Yu Wang,Feizhen Wu,Yanping Xi,Lan Zhang,Chao Ding,Huaibing Luo,Yan Li,Lina Peng,Liping Zhao,Shaoliang Peng,Yao Xiao,Shihua Dong,Jie Cao,Wenqiang Yu +16 more
TL;DR: This work focused on miR-24-1 and found that this miRNA unconventionally activates gene transcription by targeting enhancers, and demonstrates a novel mechanism of miRNA as an enhancer trigger.
References
More filters
Journal ArticleDOI
MicroRNAs: Genomics, Biogenesis, Mechanism, and Function
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
Journal ArticleDOI
A microRNA polycistron as a potential human oncogene
Lin He,J. Michael Thomson,Michael T. Hemann,Eva Hernando-Monge,David Mu,Summer G. Goodson,Scott Powers,Carlos Cordon-Cardo,Scott W. Lowe,Gregory J. Hannon,Scott M. Hammond +10 more
TL;DR: It is found that the levels of the primary or mature microRNAs derived from the mir-17–92 locus are often substantially increased in human B-cell lymphomas, and the cluster is implicate as a potential human oncogene.
Journal ArticleDOI
RAS Is Regulated by the let-7 MicroRNA Family
Steven M. Johnson,Helge Grosshans,Jaclyn Shingara,Mike Byrom,Rich Jarvis,Angie Cheng,Emmanuel Labourier,Kristy L. Reinert,David Brown,Frank J. Slack +9 more
TL;DR: It is shown that the let-7 family negatively regulates let-60/RAS, a regulatory RNAs found in multicellular eukaryotes, including humans, where they are implicated in cancer.
Journal ArticleDOI
Human MicroRNA Targets
Bino John,Anton J. Enright,Anton J. Enright,Alexei A. Aravin,Thomas Tuschl,Chris Sander,Debora S. Marks +6 more
TL;DR: This work has predicted target sites on the 3′ untranslated regions of human gene transcripts for all currently known 218 mammalian miRNAs to facilitate focused experiments and suggests that miRNA genes, which are about 1% of all human genes, regulate protein production for 10% or more of allhuman genes.
Journal ArticleDOI
MicroRNA targets in Drosophila
TL;DR: The results reaffirm the thesis that miRNAs have an important role in establishing the complex spatial and temporal patterns of gene activity necessary for the orderly progression of development and suggest additional roles in the function of the mature organism.