Open AccessLoss of RDM1 enhances hepatocellular carcinoma progression via p53 and Ras/Raf/ERK pathways
Author(s) -
Chen ShiLu,
Liu LiLi,
Wang ChunHua,
Lu ShiXun,
Yang Xia,
He YangFan,
Zhang Chris Zhiyi,
Yun JingPing
Publication year - 2020
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12593
Subject(s) - gene knockdown , cancer research , mapk/erk pathway , biology , cell growth , hepatocellular carcinoma , cell cycle , phosphorylation , cell , microbiology and biotechnology , cell culture , genetics
Hepatocellular carcinoma (HCC), with its ineffective therapeutic options and poor prognosis, represents a global threat. In the present study, we show that RAD52 motif 1 (RDM1), a key regulator of DNA double‐strand break repair and recombination, is downregulated in HCC tissues and suppresses tumor growth. In clinical HCC samples, low expression of RDM1 correlates with larger tumor size, poor tumor differentiation, and unfavorable survival. In vitro and in vivo data demonstrate that knockdown of RDM1 increases HCC cell proliferation, colony formation, and cell population at G2/M phase, whereas RDM1 overexpression results in the opposite phenotypes. Mechanistically, RDM1 binds to the tumor suppressor p53 and enhances its protein stability. In the presence of p53, RDM1 suppresses the phosphorylation of Raf and ERK. Overexpression of p53 or treatment with ERK inhibitor significantly abolishes cell proliferation induced by the depletion of RDM1. In addition, overexpression of methyltransferase‐like 3 markedly induces N6‐methyladenosine modification of RDM1 mRNA and represses its expression. Taken together, our study indicates that RDM1 functions as a tumor suppressor and may be a potential prognostic and therapeutic factor for HCC.