Downregulation of USP12 inhibits tumor growth via the p38/MAPK pathway in hepatocellular carcinoma

Liu,Chunsheng; Li,Xiaoning; Feng,Gang; Cao,Minggang; Liu,Fahu; Zhang,Guihua; Lu,Yong

doi:10.3892/mmr.2020.11557

Downregulation of USP12 inhibits tumor growth via the p38/MAPK pathway in hepatocellular carcinoma

Authors:
- Chunsheng Liu
- Xiaoning Li
- Gang Feng
- Minggang Cao
- Fahu Liu
- Guihua Zhang
- Yong Lu
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Affiliations: Department of Laboratory Medicine, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241002, P.R. China, Department of Laboratory Medicine, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241002, P.R. China, Department of Medicine, Anhui College of Traditional Chinese Medicine, Wuhu, Anhui 241000, P.R. China, School of Laboratory Medicine, Wannan Medical College, Wuhu, Anhui 241002, P.R. China
Published online on: October 1, 2020 https://doi.org/10.3892/mmr.2020.11557
Pages: 4899-4908

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Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Ubiquitin‑specific protease 12 (USP12) is specifically upregulated in the tumor tissues of patients with HCC compared with the corresponding adjacent normal tissues. However, the relationship between USP12 and the growth of HCCs is not fully understood. In the present study, USP12 was knocked down in HCC cell lines to investigate its effects on proliferation and apoptosis. The results showed that USP12‑knockdown could inhibit the proliferation and promote apoptosis in HCC cell lines. Flow cytometry analysis also showed that USP12 could induce cell cycle arrest at the G2/M stage. In vivo experiments showed that USP12‑knockdown could suppress tumor growth in mice, and immuno‑blotting revealed that USP12 could induce G2/M arrest through the cyclin dependent kinase 1/cyclinB1 axis, and trigger apoptosis via the p38/mitogen‑activated protein kinase pathway. These data strongly indicate that USP12 is a potential target for the treatment of HCC.

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