| First Author | Wei T | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 7 | Pages | 112704 |
| PubMed ID | 37379215 | Mgi Jnum | J:338536 |
| Mgi Id | MGI:7513767 | Doi | 10.1016/j.celrep.2023.112704 |
| Citation | Wei T, et al. (2023) Loss of Mettl3 enhances liver tumorigenesis by inducing hepatocyte dedifferentiation and hyperproliferation. Cell Rep 42(7):112704 |
| abstractText | While a few works have shown that Mettl3 plays oncogenic roles in hepatocellular carcinoma (HCC), its function in early HCC tumorigenesis remains unclear. In Mettl3(flox/flox); Alb-Cre knockout mice, Mettl3 loss leads to aberrant hepatocyte homeostasis and liver damage. Importantly, Mettl3 deletion dramatically accelerates liver tumorigenesis in various HCC mouse models. Depletion of Mettl3 in adult Mettl3(flox/flox) mice through TBG-Cre administration also enhances liver tumor development, while overexpression of Mettl3 inhibits hepatocarcinogenesis. Mechanistically, aggravated tumorigenesis upon Mettl3 deletion is a consequence of hepatocyte dedifferentiation and hyperproliferation via m(6)A-mediated modulation on Hnf4alpha and cell cycle genes. In contrast, by using Mettl3(flox/flox); Ubc-Cre mice, depletion of Mettl3 in established HCC ameliorates tumor progression. Additionally, Mettl3 is overexpressed in HCC tumors compared with adjacent non-tumor tissues. The present findings define a tumor-suppressive role of Mettl3 in liver tumorigenesis, indicating its potentially opposite stage-dependent functions in HCC initiation versus progression. |
