URM1 Promoted Tumor Growth and Suppressed Apoptosis via the JNK Signaling Pathway in Hepatocellular Carcinoma

Xin Cheng; Yu Zhang; Fei Song; Fengliang Song; Cheng Gao; Xiaoliang Liang; Feiran Wang; Zhong Chen

doi:10.2147/OTT.S258843

URM1 Promoted Tumor Growth and Suppressed Apoptosis via the JNK Signaling Pathway in Hepatocellular Carcinoma

Onco Targets Ther. 2020 Aug 12:13:8011-8025. doi: 10.2147/OTT.S258843. eCollection 2020.

Authors

Xin Cheng^#^{1

2}, Yu Zhang^#^{1

2}, Fei Song^{1

2}, Fengliang Song^{1

2}, Cheng Gao^{1

2}, Xiaoliang Liang^{1

2}, Feiran Wang^{1

2}, Zhong Chen¹

Affiliations

¹ Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Nantong 226001, People's Republic of China.
² Medical College of Nantong University, Nantong 226001, People's Republic of China.

^# Contributed equally.

Abstract

Objective: Ubiquitin-related modifier 1 (URM1) is a member of the ubiquitin-like regulator family, which acts as a post-translational protein modifier in the oxidative emergency response mechanism. Previous studies have shown that URM1 may be involved in the process of apoptosis and may play a role in JNK signaling pathway. In this study, we aimed to investigate the role and possible mechanism of URM1 in HCC progression.

Patients and methods: Expression of URM1 was determined in 90 pairs of matched liver cancer and adjacent non-cancerous tissues by immunohistochemistry. The impacts of URM1 on HCC cell proliferation, apoptosis, migration and invasion capacities were verified by CCK-8, colony formation, TUNEL staining, wound healing assay and transwell, respectively. Then, the effect of URM1 on subcutaneous tumor formation in vitro was explored by nude mouse xenograft model of liver cancer. Finally, the expression of apoptosis-related proteins was analyzed in URM1 knockdown samples by Western blotting.

Results: In this study, compared with paired adjacent non-cancerous tissues, the expression of URM1 was higher in liver cancer tissues (P <0.01). Kaplan-Meier survival analysis showed that high URM1 expression was significantly associated with poor prognosis (P <0.05). Moreover, URM1 knockdown inhibited liver cancer cell proliferation and migration. Furthermore, URM1 knockdown promoted apoptosis of liver cancer cells. At the same time, URM1 knockdown inhibited tumor growth in nude mouse xenograft model of liver cancer. In addition, URM1 knockdown downregulated the expression of the apoptosis-related factors JNK1/2 and TP53 and upregulated the phosphorylation of JNK1/2 and P53.

Conclusion: In summary, our results suggested that URM1 expression is increased in liver cancer tissues, and URM1 knockdown inhibits the proliferation and migration of liver cancer cells and accelerates apoptosis. High URM1 expression is associated with poor prognosis in patients with HCC.

Keywords: JNK signaling pathway; URM1; apoptosis; hepatocellular carcinoma; migration; proliferation.

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (NO. 81871927), the Jiangsu Science and Technology Department Project (BL2014060) and the Nantong Hepatobiliary and Pancreatic Surgery Disease Research Center Construction Project (HS2015001).