The serine/threonine protein phosphatase family has been demonstrated involved in a variety of cellular processes. Here, we identified that protein phosphatase, Mg2+/Mn2+ -dependent 1G (PPM1G) is an oncogene-associated protein in hepatocellular carcinoma (HCC), and is associated with the progression of HCC. In this study, we carried out a series of in vitro (MTT, colony formation, immunoblot analysis, IHC, and Q-PCR) as well as in vivo (Hepatocellular carcinoma cell xenograft mouse model) experiments to determine the biological roles of PPM1G in HCC. Our results showed that PPM1G expression was significantly increased in HCC tissues, compared with the adjacent non-tumorous tissues. Further analysis revealed that high expression of PPM1G is associated with advanced clinical characters including advanced clinical stage and tumor recurrence. Kaplan-Meier analysis suggested that a high level of PPM1G is correlated to unfavorable overall survival (P < 0.0001) as well as disease-free survival (P = 0.004) in patients with HCC. Furthermore, overexpression of PPM1G promoted cell proliferation while this effect can be attenuated by the knockdown of PPM1G in in vitro and in vivo studies. Notably, our findings showed that the tumor suppressor gene expression (e.g. pRb phosphorylation and p53 protein) was inhibited upon the silencing of PPM1G. Taken together, our study demonstrated that PPM1G plays an crucial role in HCC cell proliferation by modulating pRb phosphorylation as well as p53 expression. Furthermore, this study provides strong clinical implications of PPM1G in prognostic prediction in patients with HCC.

Citation Format: Wen Hu, Xin Yuan Guan, Lei Li, Yinghui Zhu, Yan Li, Ting Ting Zeng, Yun Fei Wen. Protein phosphatase, Mg2+/Mn2+ dependent 1G promotes proliferation via modulating phosphorylation of retinoblastoma protein and associates with poor outcome in hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 295.