USP35 promotes hepatocellular carcinoma progression by protecting PKM2 from ubiquitination‑mediated degradation

Lv,Tao; Zhang,Bo; Jiang,Chenghao; Zeng,Qiwen; Yang,Jiayin; Zhou,Yongjie

doi:10.3892/ijo.2023.5561

USP35 promotes hepatocellular carcinoma progression by protecting PKM2 from ubiquitination‑mediated degradation

Authors:
- Tao Lv
- Bo Zhang
- Chenghao Jiang
- Qiwen Zeng
- Jiayin Yang
- Yongjie Zhou
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Affiliations: Laboratory of Liver Transplantation, Frontiers Science Center for Disease‑Related Molecular Network, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China, Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: August 14, 2023 https://doi.org/10.3892/ijo.2023.5561
Article Number: 113
Copyright: © Lv et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary liver cancer with a high mortality rate and imposes a huge burden on patients and society. Recently, ubiquitin‑specific protease 35 (USP35) was found to be involved in cell proliferation and mitosis, but its role in HCC remains largely unknown. The expression of USP35 in HCC and its association with patient prognosis in the study cohort and public databases was analyzed in the present study. The effects of USP35 on the malignant biological behavior of HCC were analyzed by cellular functional experiments. Mechanistically, the effect of USP35 deubiquitylation on the M2 splice isoform of pyruvate kinase (PKM2) and on the Warburg effect of tumor cells were verified by western blotting and ubiquitination assay. The results of the present study demonstrated that USP35 is highly expressed in HCC and its high expression is significantly associated with poor prognosis of patients with HCC. In the present study, it was also demonstrated that inhibiting the expression of USP35 can impair the malignant properties (proliferation, migration and invasion) of HCC tumor cells by elevating the ubiquitination level of PKM2, the deubiquitinated form of which is critical for glycolysis in tumor cells. The present study therefore indicated that USP35 may be a target in the treatment of HCC.

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