An E2F/miR-20a Autoregulatory Feedback Loop*

By Y. Sylvestre, Vincent De Guire, E. Querido, U. Mukhopadhyay, V. Bourdeau, François Major, G. Ferbeyre, P. Chartrand. Journal of Biological Chemistry, 2007

639 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e1bb36d2e650f37924eb7cce1dc2572ad3fe3156

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Citations in the corpus

Global and Local Architecture of the Mammalian microRNA–Transcription Factor Regulatory Network (2007, background): “E2F1, 2, and 3 were shown to directly upregulate the expression of the miRs encoded in this cluster, while these miRs in turn were shown to act in a feedback loop and to target E2F1–3 mRNAs [42,43].”
MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. (2007, background): “Subsequently, several groups (31, 32) have shown the autoloop nature of the regulation of mir-17-5p, MYC, and the E2F* family of transcription factors.”
MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals. (2007, background): “The c-Myc/ E2F1/miR-17-92 network (O’Donnell et al., 2005; Sylvestre et al., 2006) is a good example of such a circuit (Figure 6D), where the MNFLs may prevent noise-driven Figure 6.”
An overview of microRNAs (2015, background): “Early work in the field focused on transcriptional regulation of miRNA host genes[25, 26, 117, 118].”
MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death (2008, background): “, 2005), E2F2 and E2F3 (Sylvestre et al., 2007), and all three E2Fs regulate the expression of miR-17-92 through binding to its promoter, suggesting an autoregulatory feedback loop.”
MicroRNA: Biogenesis, Function and Role in Cancer (2010, background): “the 3’UTR of E2F transcription factors to inhibit their translation [67-69].”
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The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease (2013, positive): “Lastly, miR-20a targets the 30UTRs of both E2F2 and E2F3 (Figure 4).(19) The ability of the cluster’s members to cooperate is evident in the context of TGF-b signaling.”
miRiad roles for the miR-17-92 cluster in development and disease. (2008, background): “E2F1, E2F2, and E2F3—activating E2Fs that induce expression of genes that drive progression from G 1 into S phase—were among the first experimentally verified targets of the miR-17-92 cluster (O’Donnell et al., 2005; Sylvestre et al., 2007; Woods et al., 2007).”
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