An E2F/miR-20a autoregulatory feedback loop.

Yannick Sylvestre; Vincent De Guire; Emmanuelle Querido; Utpal K Mukhopadhyay; Véronique Bourdeau; François Major; Gerardo Ferbeyre; Pascal Chartrand

doi:10.1074/jbc.m608939200

PubMed · 17135249

An E2F/miR-20a autoregulatory feedback loop.

Yannick Sylvestre·Vincent De Guire·Emmanuelle Querido·Utpal K Mukhopadhyay·Véronique Bourdeau·François Major·Gerardo Ferbeyre·Pascal Chartrand

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Abstract

The E2F family of transcription factors is essential in the regulation of the cell cycle and apoptosis. While the activity of E2F1-3 is tightly controlled by the retinoblastoma family of proteins, the expression of these factors is also regulated at the level of transcription, post-translational modifications and protein stability. Recently, a new level of regulation of E2Fs has been identified, where micro-RNAs (miRNAs) from the mir-17-92 cluster influence the translation of the E2F1 mRNA. We now report that miR-20a, a member of the mir-17-92 cluster, modulates the translation of the E2F2 and E2F3 mRNAs via binding sites in their 3'-untranslated region. We also found that the endogenous E2F1, E2F2, and E2F3 directly bind the promoter of the mir-17-92 cluster activating its transcription, suggesting an autoregulatory feedback loop between E2F factors and miRNAs from the mir-17-92 cluster. Our data also point toward an anti-apoptotic role for miR-20a, since overexpression of this miRNA decreased apoptosis in a prostate cancer cell line, while inhibition of miR-20a by an antisense oligonucleotide resulted in increased cell death after doxorubicin treatment. This anti-apoptotic role of miR-20a may explain some of the oncogenic capacities of the mir-17-92 cluster. Altogether, these results suggest that the autoregulation between E2F1-3 and miR-20a is important for preventing an abnormal accumulation of E2F1-3 and may play a role in the regulation of cellular proliferation and apoptosis.

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Cell Death Cell Line, Tumor Doxorubicin E2F Transcription Factors Feedback, Physiological Humans MicroRNAs Models, Chemical Oligonucleotides, Antisense Promoter Regions, Genetic RNA, Messenger Transcriptional Activation Journal Article Research Support, Non-U.S. Gov't

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Yannick Sylvestre, Vincent De Guire, Emmanuelle Querido, Utpal K Mukhopadhyay, Véronique Bourdeau, François Major, Gerardo Ferbeyre, Pascal Chartrand. 2006-11-29. An E2F/miR-20a autoregulatory feedback loop.. https://doi.org/10.1074/jbc.m608939200

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