PSME4 Activates mTOR Signaling and Promotes the Malignant Progression of Hepatocellular Carcinoma

Sijia Ge; Hua Huang; Wei Huang; Ran Ji; Jing Chen; Shuzhen Wu; Liyang Wang; Tianxin Huang; Yu Sheng; Haiou Yan; Cuihua Lu; Lin Ma

doi:10.2147/IJGM.S344360

PSME4 Activates mTOR Signaling and Promotes the Malignant Progression of Hepatocellular Carcinoma

Int J Gen Med. 2022 Jan 26:15:885-895. doi: 10.2147/IJGM.S344360. eCollection 2022.

Authors

Sijia Ge^#¹, Hua Huang^#², Wei Huang¹, Ran Ji¹, Jing Chen¹, Shuzhen Wu¹, Liyang Wang¹, Tianxin Huang¹, Yu Sheng¹, Haiou Yan¹, Cuihua Lu¹, Lin Ma³

Affiliations

¹ Department of Gastroenterology, Affiliated Hospital of Nantong University, Jiangsu, People's Republic of China.
² Department of Pathology, Affiliated Hospital of Nantong University, Jiangsu, People's Republic of China.
³ Department of Gastroenterology, Affiliated Haian Hospital of Nantong University, Jiangsu, People's Republic of China.

^# Contributed equally.

Abstract

Background: As hepatocellular carcinoma (HCC) having the second-highest mortality rate globally, the early diagnosis and prognosis of HCC have always been the focus of various studies. Although PSME4 has been reported to be closely related to several malignancies, its role in HCC remains unclear.

Materials and methods: The TCGA-LIHC database and HCC tissues were used to explore the expression of PSME4 in HCC. Gene set enrichment analysis (GSEA) was used to forecast the biological behavior of HCC cells that PSME4 might be involved in regulation. In addition, CCK-8, colony formation and flow cytometry assays were used to explore the effect of PSME4 on HCC cells. Furthermore, the underlying PSME4-related signaling pathways in HCC were further confirmed using GSEA.

Results: We found that the expression of PSME4 in HCC tissues was significantly higher than that in adjacent normal tissues, and patients with high PSME4 expression have a poor prognosis. CCK-8, colony formation and flow cytometry assays shown that knockdown of PSME4 inhibits HCC cell proliferation of HCC cells, promotes cell apoptosis and moves the cell cycle away from the S phase. Mechanistically, PSME4 may promote the development of HCC through mTOR signaling pathway.

Conclusion: The high expression of PSME4 in HCC promotes the proliferation of HCC cells via the mTOR signalling pathway. Therefore, PSME4 is an emerging tumour marker for the early diagnosis and prognosis of HCC.

Keywords: PSME4; hepatocellular carcinoma; liver cancer prognosis; mTOR signaling.

Grants and funding

This study was supported by grants from the Project supported by the National Natural Science Foundation of China (Grant No. 82070624); Social Development Foundation of Nantong City (Grant No. JC2019032; MS12019020); the Key Research and Development Plan of Jiangsu Province (No. BE2019692); Postdoctoral Science Foundation of China (Grant No. 2019M661909); Young Medical Talent Project of Jiangsu Province (QNRC2016697); Development Foundation of Nantong City (Grant No. MS12020013).