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

Mei Chee Tai, Taisuke Kajino, Masahiro Nakatochi, Chinatsu Arima, Yukako Shimada, Motoshi Suzuki, Hiroyuki Miyoshi, Yasushi Yatabe, Kiyoshi Yanagisawa, Takashi Takahashi

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1464-1473
Number of pages10
JournalCarcinogenesis
Volume36
Issue number12
DOIs
Publication statusPublished - 01-12-2015

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MicroRNAs
Lung Neoplasms
Neoplasms
Messenger RNA
Oncogenes
Japan
Cell Line
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Tai, M. C., Kajino, T., Nakatochi, M., Arima, C., Shimada, Y., Suzuki, M., ... Takahashi, T. (2015). miR-342-3p regulates MYC transcriptional activity via direct repression of E2F1 in human lung cancer. Carcinogenesis, 36(12), 1464-1473. https://doi.org/10.1093/carcin/bgv152
Tai, Mei Chee ; Kajino, Taisuke ; Nakatochi, Masahiro ; Arima, Chinatsu ; Shimada, Yukako ; Suzuki, Motoshi ; Miyoshi, Hiroyuki ; Yatabe, Yasushi ; Yanagisawa, Kiyoshi ; Takahashi, Takashi. / miR-342-3p regulates MYC transcriptional activity via direct repression of E2F1 in human lung cancer. In: Carcinogenesis. 2015 ; Vol. 36, No. 12. pp. 1464-1473.
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Tai, MC, Kajino, T, Nakatochi, M, Arima, C, Shimada, Y, Suzuki, M, Miyoshi, H, Yatabe, Y, Yanagisawa, K & Takahashi, T 2015, 'miR-342-3p regulates MYC transcriptional activity via direct repression of E2F1 in human lung cancer', Carcinogenesis, vol. 36, no. 12, pp. 1464-1473. https://doi.org/10.1093/carcin/bgv152

miR-342-3p regulates MYC transcriptional activity via direct repression of E2F1 in human lung cancer. / Tai, Mei Chee; Kajino, Taisuke; Nakatochi, Masahiro; Arima, Chinatsu; Shimada, Yukako; Suzuki, Motoshi; Miyoshi, Hiroyuki; Yatabe, Yasushi; Yanagisawa, Kiyoshi; Takahashi, Takashi.

In: Carcinogenesis, Vol. 36, No. 12, 01.12.2015, p. 1464-1473.

Research output: Contribution to journalArticle

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T1 - miR-342-3p regulates MYC transcriptional activity via direct repression of E2F1 in human lung cancer

AU - Tai, Mei Chee

AU - Kajino, Taisuke

AU - Nakatochi, Masahiro

AU - Arima, Chinatsu

AU - Shimada, Yukako

AU - Suzuki, Motoshi

AU - Miyoshi, Hiroyuki

AU - Yatabe, Yasushi

AU - Yanagisawa, Kiyoshi

AU - Takahashi, Takashi

PY - 2015/12/1

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