From Data Mining to Functional Validation: UBE2S Regulates Proliferation and Radiosensitivity in Colorectal Cancer via the PI3K/AKT Pathway

Background Colorectal cancer is the third most common malignant tumor worldwide, accounting for approximately 10% of all newly diagnosed cancer cases annually. UBE2S has been demonstrated to play an oncogenic role in various types of cancer. however, its specific mechanism in colorectal cancer remains poorly understood. Methods In this study, we initially identified the differential expression of UBE2S between colorectal cancer tissues and normal colorectal tissues from patients by analyzing data from TCGA and GEO databases. Meanwhile, UBE2S also exhibits certain significance in pan-cancer. Further studies showed that compared with normal colorectal epithelial cells, UBE2S was highly expressed in colorectal cancer cells and had a certain correlation with immune infiltrating cells. We then investigated the effects of UBE2S knockdown and overexpression on the proliferation and radiotherapy sensitivity of colorectal cancer cells. RNA sequencing analysis revealed that UBE2S was enriched in pathways related to cell cycle, apoptosis, PI3K/AKT signaling, DNA replication, base excision repair, ferroptosis, and non-homologous end joining. Subsequently, we evaluated the changes in PI3K/AKT pathway-related proteins after UBE2S knockout and overexpression, as well as the effect of the PI3K/AKT pathway inhibitor LY294002 on the proliferation of colorectal cancer cells. Results The results showed that UBE2S is highly expressed in colorectal cancer and has a certain correlation with immune infiltrating cells. UBE2S promotes the proliferation and radiotherapy resistance of colorectal cancer cells; meanwhile, overexpression of UBE2S can activate the PI3K/AKT pathway, and this effect can be reversed by the addition of LY294002. In conclusion, our findings suggest that UBE2S may promote the proliferation and radiotherapy resistance of colorectal cancer cells by activating the PI3K/AKT signaling pathway. Conclusion In this study, we believe that UBE2S acts as an oncogene in colorectal cancer and can promote the progression of colorectal cancer by activating the PI3K/AKT pathway. The study of UBE2S not only contributes to a deeper understanding of the molecular mechanisms of colorectal cancer but also provides potential targets and strategies for clinical treatment. Intervention targeting UBE2S may improve the prognosis and treatment outcomes of colorectal cancer patients.