Identification of a novel microRNA-mRNA regulatory biomodule in human prostate cancer

Cell Death & Disease
Yan-Qiong ZhangNa Lin

Abstract

Our recent study identified a list of differentially expressed microRNAs (miRNAs) in human prostate cancer (PCa) tissues compared to adjacent benign prostate tissues. In the current study, to identify the crucial miRNA-mRNA regulatory biomodule involved into prostate carcinogenesis based on the previous miRNA expression profile in PCa, we proposed an integrated systematic approach which combined miRNA-mediated gene expression regulatory network analysis, experimental validations in vitro and in vivo, as well as clinical significance evaluation. As a result, the CCND1-RNASEL-CDKN1A-TP73-MDM2-UBE2I axis was identified as a bottleneck in the miRNA-mediated gene expression regulatory network of PCa according to network topological analysis. The direct binding relationship between TP73 and PCa downregulated miR-193a-5p, and the direct binding relationship between UBE2I and PCa upregulated miR-188-5p were both experimentally validated. In addition, miR-193a-5p had a more significant regulatory effect on the tumor promoter isoform of TP73-deltaNp73 than on the tumor suppressive isoform of TP73-TAp73. Importantly, the deregulation of either the miR-193a-5p-TP73 or miR-188-5p-UBE2I axes was significantly associated with aggressive progr...Continue Reading

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Citations

Sep 7, 2018·Journal of Experimental & Clinical Cancer Research : CR·Sen-Mao LiJia Hu
Jun 25, 2020·Cancer Metastasis Reviews·Belinda J Petri, Carolyn M Klinge
Dec 21, 2018·Molecular Medicine Reports·Shuilong ZhangDongliang Wang
Dec 29, 2020·Cancer Biomarkers : Section a of Disease Markers·Angelika TölleCarsten Stephan
May 27, 2021·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Liang BaiJianfeng Huang

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Methods Mentioned

BETA
two-hybrid
ubiquitination
xenografts
transfection
xenograft
reverse transcription-PCR

Software Mentioned

miRWalk
TargetScan
miRanda
SPSS
R

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