PPM1G promotes cell proliferation via modulating mutant GOF p53 protein expression in hepatocellular carcinoma

Wen Hu; Shao-Lin Ma; Liang Qiong; Yu Du; Li-Ping Gong; Yu-Hang Pan; Li-Ping Sun; Jing-Yun Wen; Jian-Ning Chen; Xin-Yuan Guan; Chun-Kui Shao

doi:10.1016/j.isci.2024.109116

PPM1G promotes cell proliferation via modulating mutant GOF p53 protein expression in hepatocellular carcinoma

iScience. 2024 Feb 5;27(3):109116. doi: 10.1016/j.isci.2024.109116. eCollection 2024 Mar 15.

Authors

Wen Hu¹, Shao-Lin Ma², Liang Qiong¹, Yu Du¹, Li-Ping Gong¹, Yu-Hang Pan¹, Li-Ping Sun¹, Jing-Yun Wen³, Jian-Ning Chen¹, Xin-Yuan Guan^{4

5

6}, Chun-Kui Shao¹

Affiliations

¹ Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
² Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China.
³ Department of Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
⁴ State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
⁵ Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
⁶ Department of Clinical Oncology, the University of Hong Kong, Hong Kong, China.

Abstract

The serine/threonine protein phosphatase family involves series of cellular processes, such as pre-mRNA splicing. The function of one of its members, protein phosphatase, Mg²⁺/Mn2+ dependent 1G (PPM1G), remains unclear in hepatocellular carcinoma (HCC). Our results demonstrated that PPM1G was significantly overexpressed in HCC cells and tumor tissues compared with the normal liver tissues at both protein and RNA levels. High PPM1G expression is associated with shorter overall survival (p < 0.0001) and disease-free survival (p = 0.004) in HCC patients. Enhanced expression of PPM1G increases the cell proliferation rate, and knockdown of PPM1G led to a significant reduction in tumor volume in vivo. Further experiments illustrated that upregulated-PPM1G expression increased the protein expression of gain-of-function (GOF) mutant p53. Besides, the immunoprecipitation analysis revealed a direct interaction between PPM1G and GOF mutant p53. Collectively, PPM1G can be a powerful prognostic predictor and potential drug-target molecule.

Keywords: Biochemistry; Genetics; Molecular genetics.