口腔鳞状细胞癌是今朝头颈部最多见的恶性肿瘤,但其发生发展的机制尚不清楚,仍然缺乏有效的靶向药物。DNA聚合酶的第二个主要亚基(POLE2)具有外切核酸酶活性,可以催化新链的复制和修饰。我们以前的研究发现它与OSCC进展有关,但机制尚不清楚。用免疫学方法检测POLE2在OSCC中的表达。POLE2在OSCC细胞中的表达受到抑制,通过RT-PCR和WesternBlot检测细胞的生物学功能。细胞增殖,通过集落形成检测到细胞凋亡和迁移,MTT,流式细胞术,伤口愈合和Transwell。POLE2基因在OSCC中的表达程度明显高于正常组织。此外,POLE2基因的表达水平与肿瘤类型和预后有显著差异。在口腔鳞状细胞癌的发展过程中,沉默POLE2抑制口腔癌细胞增殖,促进细胞凋亡。动物实验的结果也支持POLE2与OSCC进展之间的正相关。我们进一步证明POLE2可以上调凋亡相关蛋白如Caspase3、CD40、CD40L、DR6,Fas,IGFBP-6、P21和SMAC。此外,POLE2通过抑制PI3K/AKT通路调节OSCC进展。POLE2与OSCC的进展密切相关,POLE2可能是OSCC治疗的潜在靶点。
Oral squamous cell carcinoma is the most common malignant tumor in the head and neck at present, but the mechanism of its occurrence and development is still unclear, and there is still a lack of effective targeting drugs. The second major subunit of DNA polymerase (
POLE2) has exonuclease activity and can catalyze the replication and modification of new chains. Our previous studies have found that it is associated with OSCC progression, but the mechanism is unclear.The expression of POLE2 in OSCC was detected by immunological method. The expression of POLE2 was inhibited in OSCC cells, and the biological function of the cells 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. The expression level of
POLE2 gene in OSCC was significantly higher than that in normal tissues. In addition, the expression level of POLE2 gene was significantly different from the tumor type and prognosis. During the development of oral squamous cell carcinoma, silencing
POLE2 inhibits the proliferation of oral cancer cells and promotes apoptosis. The results of animal experiments also support the positive correlation between POLE2 and OSCC progression. We further demonstrated that POLE2 can up-regulate the downregulation of apoptosis-related proteins such as Caspase3, CD40, CD40L, DR6, Fas, IGFBP-6, P21, and SMAC. In addition,
POLE2 regulates OSCC progression by inhibiting the PI3K/AKT pathway.
POLE2 is closely related to the progression of OSCC, and
POLE2 may be a potential target for OSCC treatment.