METTL5-mediated 18S rRNA m⁶A modification promotes oncogenic mRNA translation and intrahepatic cholangiocarcinoma progression.

ABSTRACT: Intrahepatic cholangiocarcinoma (ICC) is a deadly cancer with rapid tumor progression. While hyperactive mRNA translation caused by mis-regulated mRNA or tRNA modifications promotes ICC development, the role of rRNA modifications remains elusive. Here, we found that 18S rRNA m⁶A modification and its methyltransferase METTL5 were aberrantly upregulated in ICC and associated with poorer survival (log rank test, p < 0.05). We further revealed the critical role of METTL5-mediated 18S rRNA m⁶A modification in regulation of ICC cell growth and metastasis using loss- and gain-of function assays in vitro and in vivo. The oncogenic function of METTL5 is corroborated using liver-specific knockout and overexpression ICC mouse models. Mechanistically, METTL5 depletion impairs 18S

SUBMITTER: Dai Z 

PROVIDER: S-EPMC10638452 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature