miR-342-3p regulates MYC transcriptional activity via direct repression of E2F1 in human lung cancer.

Abstract

Accumulating evidence indicates that altered miRNA expression is crucially involved in lung cancer development, though scant information is available regarding how MYC, an archetypical oncogene, is regulated by miRNAs, especially via a mechanism involving MYC cofactors. In this study, we attempted to identify miRNAs involved in regulation of MYC transcriptional activity in lung cancer. To this end, we utilized an integrative approach with combinatorial usage of miRNA and mRNA expression profile datasets of patient tumor tissues, as well as those of MYC-inducible cell lines in vitro. In addition to miRNAs previously reported to be directly regulated by MYC, including let-7 and miR-17-92, our strategy also helped to identify miR-342-3p as capable of indirectly regulating MYC activity via direct repression of E2F1, a MYC-cooperating molecule. Furthermore, miR-342-3p module activity, which we defined as a gene set reflecting the experimentally substantiated influence of miR-342-3p on mRNA expression, was found to be inversely correlated with MYC activity reflected by MYC module activity in three independent datasets of lung adenocarcinoma patients obtained from the Director's Challenge Consortium of the United States (P = 1.94 × 10(-73)), the National Cancer Center of Japan (P = 9.05 × 10(-34)) and the present study (P = 1.17 × 10(-19)). Our integrative approach appears to be useful to elucidate inter-regulatory relationships between miRNAs and protein coding genes of interest, even those present in patient tumor tissues, which remains a challenge to better understand the pathogenesis of this devastating disease.

• Authors: Mei Chee Tai, Taisuke Kajino, Masahiro Nakatochi, Chinatsu Arima, Yukako Shimada, Motoshi Suzuki, Hiroyuki Miyoshi, Yasushi Yatabe, Kiyoshi Yanagisawa, Takashi Takahashi
• Journal: Carcinogenesis (Carcinogenesis) Vol. 36 Issue 12 Pg. 1464-73 (Dec 2015) ISSN: 1460-2180 [Electronic] England
• PMID: 26483346 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• 3' Untranslated Regions
• E2F1 Transcription Factor
• E2F1 protein, human
• MIRN342 microRNA, human
• MYC protein, human
• MicroRNAs
• Proto-Oncogene Proteins c-myc

Topics

• 3' Untranslated Regions
• Adenocarcinoma (genetics, metabolism)
• Adult
• Aged
• Aged, 80 and over
• Base Sequence
• Binding Sites
• Cell Line, Tumor
• E2F1 Transcription Factor (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (genetics, metabolism)
• Male
• MicroRNAs (physiology)
• Middle Aged
• Proto-Oncogene Proteins c-myc (physiology)
• RNA Interference
• Transcription, Genetic
• Transcriptional Activation