UBE2S enhances the ubiquitination of p53 and exerts oncogenic activities in hepatocellular carcinoma

Journal Article · Sat Sep 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.06.093· OSTI ID:23105678

Pan, Ying-Hua ^[1]; Yang, Mei ^[2]; Liu, Li-ping ^[3]; Wu, Dan-Chun ^[1]; Li, Ming-yue ^[3]; Su, Shu-Guang ^[4]

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1. Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou (China)
2. Department of Gastroenterology, Dongguan Third People's Hospital, Dongguan (China)
3. Department of Hepatobiliary and Pancreatic Surgery, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong Province (China)
4. Department of Pathology, The Affiliated Hexian Memorial Hospital of Southern Medical University, Guangzhou (China)

Highlights: • High expression of UBE2S is significantly correlated with poor outcomes in two independent cohorts containing 845 patients. • UBE2S promotes cell proliferation and migration in HCC. • UBE2S exerts oncogenic activities via enhancing the ubiquitination of p53. Ubiquitin-conjugating enzyme E2S (UBE2S) plays pivotal roles in the progression of human cancers. However, its clinical significance and role in hepatocellular carcinoma (HCC) remain unknown. Here, we show that UBE2S is upregulated in HCC and exhibits oncogenic activities via enhancing the ubiquitination of p53. Increased expression of UBE2S was significantly correlated with higher serum AFP level, higher pathological grade, advanced TNM stage, larger tumor size, vascular invasion and unfavorable patient survivals in two independent cohorts containing a total of 845 patients with HCC. Multivariate analyses by cox regression model suggested UBE2S as an independent factor for overall survival. In vitro experiments demonstrated that UBE2S overexpression promoted, whereas UBE2S knockdown suppressed cell proliferation and migration via modulation of p53 signaling pathway. Ectopic expression of UBE2S upregulated the expression of p53 and its downstream effectors, such as p21 and Cyclin D1. Mechanistically, UBE2S enhanced the ubiquitination of p53 protein to facilitate its degradation in HCC cells. Re-expression of p53 partially attenuated the UBE2S-promoted malignant phenotypes. Collectively, our study provides compelling evidence that UBE2S is a potential prognostic factor and functions as an oncogene in HCC.

• OSTI ID: 23105678
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 503; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL PROLIFERATION
ENZYMES
HEPATOMAS
ONCOGENES