| First Author | Lizé M | Year | 2010 |
| Journal | Cell Death Differ | Volume | 17 |
| Issue | 3 | Pages | 452-8 |
| PubMed ID | 19960022 | Mgi Jnum | J:169429 |
| Mgi Id | MGI:4940961 | Doi | 10.1038/cdd.2009.188 |
| Citation | Lize M, et al. (2010) E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis. Cell Death Differ 17(3):452-8 |
| abstractText | E2F1 is a positive regulator of cell cycle progression and also a potent inducer of apoptosis, especially when activated by DNA damage. We identified E2F1-inducible microRNAs (miRNAs) by microarray hybridization and found that the levels of miRNAs 449a and 449b, as well as their host gene CDC20B, are strongly upregulated by E2F1. High miR-449 levels were found in testes, lung, and trachea, but not in testicular and other cancer cells. MiR-449a/b structurally resemble the p53-inducible miRNA 34 family. In agreement with a putative tumor-suppressive role, miR-449a as well as miR-34a reduced proliferation and strongly promoted apoptosis by at least partially p53-independent mechanisms. Both miRNAs reduced the levels of CDK6, implying miR-449 in a negative feedback mechanism for E2F1. Moreover, miR-449a and miR-34a diminished the deacetylase Sirt1 and augmented p53 acetylation. We propose that both miRNAs provide a twofold safety mechanism to avoid excessive E2F1-induced proliferation by cell cycle arrest and by apoptosis. While responding to different transactivators, miRNAs 449 and 34 each repress E2F1, but promote p53 activity, allowing efficient cross-talk between two major DNA damage-responsive gene regulators. |
