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

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.

Active fraction from clove inhibits colorectal cancer cell proliferation by downregulating M2-type pyruvate kinase to reduce aerobic glycolysis

“…Nearly all types of cancer cells appear to overexpress PKM2 to promote aerobic glycolysis and give tumor cells a proliferative advantage over healthy tissue [38][39][40][41]. We found that the AFC downregulated the kinase in HCT116 and LoVo colon cancer cell lines in a dose-dependent manner (Fig.…”