Silencing POLE2 promotes apoptosis and inhibits proliferation of oral squamous cell carcinomasby inhibiting PI3K/AKT signaling pathway

Abstract

Abstract Background: Oral squamous cell carcinoma is the most common malignant tumor of the head and neck at present, but its occurrence and progression mechanism is still unclear, and effective targeting drugs are still lacking. The second major subunit (POLE2) of DNA polymerase catalyzes the prolongation of new strand replication and modifies the exonuclease domain activity. Our previous study found that it is associated with OSCC progression, but the mechanism remains unclear. Methods: The expression of POLE2 in OSCC tissues was detected by immunological method. POLE2 expression was inhibited in OSCC cells, and cell function was detected by RT-PCR and Western Blot. Cell proliferation, apoptosis and migration were detected by colony formation, MTT, flow cytometry, wound healing and Transwell. Results: The expression level of POLE2 gene in OSCC was significantly higher than that in normal tissues. In addition, POLE2 gene expression level was statistically correlated with tumor classification and prognosis. Silencing POLE2 during the progression of oral squamous cell carcinoma can inhibit the proliferation of oral cancer cells and promote cell apoptosis. Animal experimental results also supported a positive correlation between PORE2 and OSCC tumor formation, which was consistent with previous results. We further confirmed that POLE2 up-regulated the knockdown of apoptosis-promoting proteins (BIM) in Caspase3, CD40, CD40L, DR6, Fas, IGFBP-6, P21 and SMAC. In addition, POLE2 regulates OSCC development by inhibiting THE PI3K/AKT signaling pathway. Conclusion: POLE2 is closely related to the progress of OSCC. POLE2 may be a potential target for OSCC treatment in the future.