UBD Promotes The Proliferation and Epithelial-Mesenchymal Transition of Hepatocellular Carcinomas via Regulating CTNNA3.

Abstract

Objective: Hepatocellular carcinoma (HCC), a prevalent and aggressive malignancy, is one of the most common malignancies worldwide. Various studies show that ubiquitin D (UBD) is overexpresses in different cancer types and may serve as a potential prognostic factor. Although catenin alpha 3 (CTNNA3) is a tumour suppressor in HCC, the relationship between UBD and CTNNA3 in HCC remains unclear. This study aims to explore the role of UBD in HCC and its relationship with CTNNA3 in HCC cells.

Materials and methods: In this experimental study, UBD expression in clinical samples was analysed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Protein levels of epithelialmesenchymal transition (EMT) markers were evaluated by Western blot. Cellular behaviours that included proliferation, colony formation, migration, and invasion were assessed using the CCK-8, colony formation, EdU, and transwell assays. UBD-mediated ubiquitination of CTNNA3 was examined by in vitro ubiquitination assays.

Results: There was a significant elevation in UBD expression in the HCC patients, which correlated with poor prognosis. Knockdown of UBD suppressed the proliferation, colony formation, and EMT of the HCC cells. UBD reduced CTNNA3 expression in HCC cells by promoting the ubiquitination and degradation of CTNNA3. Decreased CTNNA3 expression in HCC patients was associated with poor overall survival. Silencing of CTNNA3 repressed HCC proliferation, migration, invasion, and EMT. CTNNA3 deficiency counteracted the inhibitory effects of UBD knockdown on the malignant behaviour of the HCC cells.

Conclusion: UBD plays an oncogenic role in HCC by encouraging proliferation and EMT through promoting CTNNA3 degradation. These findings suggest that targeting the UBD/CTNNA3 axis could be a potential therapeutic strategy for HCC management.