Hepatocyte-specific Wtap deficiency promotes hepatocellular carcinoma by activating GRB2-ERK depending on downregulation of proteasome-related genes.

ABSTRACT: Wilm's tumor 1-associating protein (WTAP), a regulatory protein of the m⁶A methyltransferase complex, has been found to play a role in regulating various physiological and pathological processes. However, the in vivo role of WTAP in the pathogenesis of hepatocellular carcinoma (HCC) is unknown. In this study, we have elucidated the crucial role of WTAP in HCC progression and shown that hepatic deletion of Wtap promotes HCC pathogenesis through activation of multiple signaling pathways. A single dose of diethylnitrosamine injection causes more and larger HCCs in hepatocyte-specific Wtap knockout (Wtap-HKO) mice than Wtap^flox/flox mice fed with either normal chow diet or a high-fat diet. Elevated CD36, IGFBP1 (insulin-like growth factor-binding protein 1), and chemokine

SUBMITTER: Li X 

PROVIDER: S-EPMC10630636 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature