AGO2 phosphorylation by c-Src kinase promotes tumorigenesis

AGO2 phosphorylation by c-Src kinase promotes tumorigenesis:
Publication date: March 2020
Source: Neoplasia, Volume 22, Issue 3
Author(s): Tianqi Liu, Hailong Zhang, Jiayu Fang, Zhi Yang, Ran Chen, Yanli Wang, Xian Zhao, Shengfang Ge, Jianxiu Yu, Jian Huang

Abstract

Numerous studies have reported that c-Src is highly expressed with high tyrosine kinase activity in a variety of tumors. However, it remains unclear whether c-Src contributes to the miRNA pathway. Here, we report that c-Src can interact with and phosphorylate AGO2, a core component of RISC complex, at tyr 393, tyr 529 and tyr749. Mechanistically, it is confirmed that c-Src phosphorylation of AGO2 at tyr393 reduces its binding to DICER, thereby suppressing the maturation of long-loop pre-miR-192. However, the other two phosphorylation sites don’t work on this function. Significantly, Ectopic expression of wild-type AGO2, but not the three tyrosine site mutants, has an obvious tumor-promoting effect in vitro and in vivo, which function could be blocked thoroughly by treatment with c-Src kinase inhibitor, Saracatinib. Our findings identify AGO2 as c-Src target and c-Src phosphorylation of AGO2 may therefore play a potential role during tumor progress.