| First Author | Wu L | Year | 2015 |
| Journal | Elife | Volume | 4 |
| Pages | e09431 | PubMed ID | 26445246 |
| Mgi Jnum | J:229614 | Mgi Id | MGI:5752687 |
| Doi | 10.7554/eLife.09431 | Citation | Wu L, et al. (2015) Precise let-7 expression levels balance organ regeneration against tumor suppression. Elife 4:e09431 |
| abstractText | The in vivo roles for even the most intensely studied microRNAs remain poorly defined. Here, analysis of mouse models revealed that let-7, a large and ancient microRNA family, performs tumor suppressive roles at the expense of regeneration. Too little or too much let-7 resulted in compromised protection against cancer or tissue damage, respectively. Modest let-7 overexpression abrogated MYC-driven liver cancer by antagonizing multiple let-7 sensitive oncogenes. However, the same level of overexpression blocked liver regeneration, while let-7 deletion enhanced it, demonstrating that distinct let-7 levels can mediate desirable phenotypes. let-7 dependent regeneration phenotypes resulted from influences on the insulin-PI3K-mTOR pathway. We found that chronic high-dose let-7 overexpression caused liver damage and degeneration, paradoxically leading to tumorigenesis. These dose-dependent roles for let-7 in tissue repair and tumorigenesis rationalize the tight regulation of this microRNA in development, and have important implications for let-7 based therapeutics. |
