USP28 promotes aerobic glycolysis of colorectal cancer by increasing stability of FOXC1

Zhaohui  Liu; Min Chen; Xiaoping  Xu; Lei  Zhang; Yuan  Pan; Dong  Chen

doi:10.18388/abp.2020_5504

Zhaohui Liu Department of Anorectal Surgery, First People’s Hospital of Yuhang District, Hangzhou, Hangzhou City, Zhejiang Province, 311100, P.R. China
Min Chen Department of Anesthesia, First People’s Hospital of Yuhang District, Hangzhou, Hangzhou City, Zhejiang Province, 311100, P.R. China https://orcid.org/0000-0003-2903-0388
Xiaoping Xu Department of Anorectal Surgery, First People’s Hospital of Yuhang District, Hangzhou, Hangzhou City, Zhejiang Province, 311100, P.R. China
Lei Zhang Department of Anorectal Surgery, First People’s Hospital of Yuhang District, Hangzhou, Hangzhou City, Zhejiang Province, 311100, P.R. China
Yuan Pan Department of Anorectal Surgery, First People’s Hospital of Yuhang District, Hangzhou, Hangzhou City, Zhejiang Province, 311100, P.R. China
Dong Chen Department of Anorectal Surgery, First People’s Hospital of Yuhang District, Hangzhou, Hangzhou City, Zhejiang Province, 311100, P.R. China

DOI: https://doi.org/10.18388/abp.2020_5504

Abstract

Aerobic glycolysis is essential for cancer cell metabolism and growth. Deubiquitinase, USP28 (ubiquitin specific peptidase 28), could maintain stability of proteins involved in tumor progression. This study was performed to investigate the role of USP28 in aerobic glycolysis of colorectal cancer. Our data showed that USP28 mRNA and protein expressions were enhanced in colorectal cancer tissues and cells. Functional assays demonstrated that overexpression of USP28 promoted cell proliferation and aerobic glycolysis of colorectal cancer, while USP28 inhibition could reverse these effects. Protein expression of Forkhead Box C1 (FOXC1) was increased by USP28 over-expression, whereas knockdown of USP28 aggravated cycloheximide (CHX; protein synthesis inhibitor) stimulated decrease of FOXC1. Moreover, proteasome inhibitor, MG132, could rescue USP28 silence-induced degradation of FOXC1. Overexpression of FOXC1 counteracted the suppressive effects of USP28 interference on colorectal cancer cell viability and aerobic glycolysis. In conclusion, USP28 enhanced cell viability and aerobic glycolysis of colorectal cancer by stabilizing FOXC1, suggesting that USP28-FOXC1 might be a novel therapeutic avenue for colorectal cancer.