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APOBEC3B promotes hepatocarcinogenesis and metastasis through novel deaminase‐independent activity
Author(s) -
Ma Wei,
Ho Daniel WH.,
Sze Karen MF.,
Tsui YuMan,
Chan LoKong,
Lee Joyce MF.,
Ng Irene OL.
Publication year - 2019
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22956
Subject(s) - biology , cytidine deaminase , cancer research , gene knockdown , hccs , metastasis , carcinogenesis , transcriptome , cell growth , cell cycle , mutation , genome instability , cell , microbiology and biotechnology , cell culture , hepatocellular carcinoma , cancer , genetics , gene , gene expression , dna damage , dna
Cytidine deaminase APOBEC3B (A3B) is known to play important roles in creating de novo genomic C‐to‐T mutations in cancers and contribute to induction of genomic instability. Our study evaluated the roles of A3B in the progression and metastasis of human hepatocellular carcinoma (HCC). Using whole‐transcriptome and whole‐exome sequencing, and quantitative PCR, we found that A3B was overexpressed in human HCCs and A3B expression was significantly correlated with the proportion of genomic C‐to‐A and G‐to‐T mutations. Upon clinicopathological correlation, higher A3B expression was associated with more aggressive tumor behavior. Wild‐type A3B (wt‐A3B) overexpression in HCC cells promoted cell proliferation, and cell migratory and invasive abilities in vitro, and tumorigenicity and metastasis in vivo. On the other hand, knockdown of A3B suppressed cell proliferation, migratory, and invasive abilities of HCC cells with high endogenous A3B level. However, to our surprise, overexpression of A3B deaminase‐dead double mutant (E68A/E255Q) led to similar results as wt‐A3B in HCC. Furthermore, overexpression of wt‐A3B and mutant A3B both enhanced cell cycle progression in HCC cells. Altogether, our data demonstrated a novel deaminase‐independent role of A3B in contributing to HCC tumorigenesis and metastasis.