线粒体相关细胞凋亡诱导因子3通过调控STAT3信号通路影响结直肠癌细胞增殖与迁移

AIFM3 interferes the proliferation and migration of colorectal cancer cells by regulating STAT3 signaling pathway

目的 探讨线粒体相关细胞凋亡诱导因子3(AIFM3)对结直肠癌细胞增殖及迁移的影响及其分子机制。方法 采用生物学信息方法预测AIFM3的表达与结直肠癌组织类型和预后的关系,用免疫组化法检测我院组织样本中AIFM3蛋白的表达,并分析其与预后的关系。利用慢病毒建立稳定干扰AIFM3表达的细胞株HCT116和SW620,并以CCK8和平板克隆实验检测细胞的增殖能力变化,以Transwell迁移实验检测细胞的迁移能力变化。Western blot法验证AIFM3基因的沉默效果及相关通路蛋白表达情况。结果 相比于癌旁组织,AIFM3在结直肠癌中的表达显著降低,且高表达组的无病生存率、总生存率显著高于低表达组(P <0.05);抑制AIFM3可显著抑制HCT116和SW620细胞的增殖和迁移能力。GSEA分析显示AIFM3与STAT3信号通路相关;而Western blot结果表明,敲低AIFM3后,STAT3、P-STAT3的蛋白表达水平显著上调。结论 AIFM3在结直肠癌组织表达显著降低。干扰HCT116和SW620细胞中AIFM3的表达可增加细胞的增殖与迁移能力,其机制可能与STAT3信号通路有关。AIFM3可作为结直肠癌的潜在治疗靶点。

Objective To explore the effect of apoptosis-inducing factor mitochondria associated 3(AIFM3)on colorectal cancer cells and its mechanism.Methods The relationship between the expression of AIFM3 and the tissue type and prognosis of colorectal cancer was detected bybio-informatics and verified by immunohistochemistry.We knockdown the expression of AIFM3 in cell lines HCT116 and SW620 by lentivirus.The silencing effect of AIFM3 gene was verified by Western blot,the proliferation ability of cells was detected by CCK8 experiment and plate cloning experiment,and the migration ability of cells was detected by transwell migration assay.Results The expression of AIFM3 in colorectal cancer was lower than that in adjacent tissues,and its expression was related to the prognosis of colorectal cancer;knockdown of AIFM3 could significantly inhibit the proliferation and migration of HCT116 and SW620 cells.GSEA analysis showed that there was a correlation between AIFM3 and STAT3 signal pathway.Western blot showed that the protein expression levels of STAT3 and p-STAT3 were significantly up-regulated after knockdown of aifm3.Conclusions The expression of aifm3 was significantly down regulated in colorectal cancer.Knockdown the expression of aifm3 in HCT116 and SW620 cells could increase cell proliferation and migration,and its mechanism may be related to STAT3 signaling pathway.