Mobile website
Basic Research
Effect and mechanism of ubiquitin-specific protease 21 on proliferation and migration of cholangiocarcinoma cells
- Article
- Figures
- Metrics
- Preview PDF
- Reference
- Related
- Cited by
- Materials
Abstract:
Objectives: To investigate the expression of ubiquitin-specific protease 21 (USP21) in cholangiocarcinoma (CCA) and its effect on the proliferation and migration of CCA cells, as well as the underlying mechanisms. Methods: The expression of USP21 in CCA tissues and cells was detected using bioinformatics approaches, immunohistochemistry, and Western blotting (WB). The effects of USP21 knockdown on the proliferation and migration of CCA cell lines (QBC939 and RBE) were assessed by in vitro colony formation, EdU, and Transwell assays. The oncogenic mechanism of USP21 was explored using RNA sequencing, mass spectrometry, co-immunoprecipitation (CO-IP), and WB. Results: Analysis of databases such as TCGA revealed that USP21 mRNA expression was significantly elevated in CCA tissues (P < 0.05) and USP21 protein expression was highly expressed in both CCA tissues and cells (P < 0.05, P < 0.01, or P < 0.001). Knockdown of USP21 led to a significant decrease in the proliferative and migratory abilities of QBC939 and RBE cells (P < 0.01 or P < 0.001). RNA sequencing results indicated that USP21 knockdown inhibited the proliferative and migratory abilities of CCA cells by suppressing the PI3K/AKT signaling pathway (P < 0.05). Mass spectrometry identified a binding between USP21 and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1). Co-IP and WB results demonstrated that USP21 interacts with IGF2BP1 and regulates its protein expression through the ubiquitination pathway (P < 0.001 or P < 0.000 1). Conclusion: USP21 is highly expressed in both CCA tissues and cells and enhances the proliferative and migratory abilities of CCA through the IGF2BP1/PI3K/AKT signaling pathway.
Keywords:
Project Supported:
Clc Number:
