Abstract The ubiquitin–proteasome system (UPS) is an important regulator of numerous cellular pathways, including DNA repair, protein degradation, the cell cycle, and signal transduction. UBE2C, a member of the ubiquitin-conjugating enzyme family, facilitates the ubiquitination of essential cellular regulators. Notably, UBE2C is consistently overexpressed in breast, lung, brain, hepatocellular, and ovarian carcinomas. Increased UBE2C expression is associated with tumour aggressiveness, genomic instability, epithelial-to-mesenchymal transition, and resistance to chemotherapy and radiotherapy. Our review explores the mechanistic involvement of UBE2C in diverse cancers, with a particular focus on its involvement in DNA damage repair mediated by the anaphase-promoting complex (APC/C). Furthermore, the regulatory effects of miR-381, miR-503, and miR-205 on UBE2C expression were examined, highlighting the promising prospects of these miRNAs for targeted cancer therapy. The involvement of UBE2C in different cancer hallmarks underscores its potential as a biomarker and therapeutic target. A comprehensive understanding of its mechanistic involvement in cell cycle regulation and DNA repair will further enhance its application in diagnostics, personalised medicine, and precision medicine. Graphical Abstract UBE2C acts as a central regulator of tumour progression by coordinating cell-cycle control, oncogenic signalling, DNA damage repair, and therapy resistance. Dysregulated UBE2C expression promotes cancer cell proliferation, survival, genome maintenance, and treatment resistance, whereas its inhibition through miRNAs, RNAi, or pharmacological agents induces cell-cycle arrest, apoptosis, and enhanced therapeutic sensitivity, supporting UBE2C as an attractive target for cancer therapy. Created with BioRender.com.
Paul et al. (2026) studied this question.