KMT2C通过c-Myc/CDK4信号通路调控胃癌细胞的生长与增殖

KMT2C Regulates Growth and Proliferation of Gastric Cancer Cells Through c-Myc/CDK4 Signaling Pathway

目的探究赖氨酸特异性甲基转移酶2C(lysine specific methyltransferase 2C,KMT2C)在胃癌发生发展中的作用及机制。方法通过TCGA数据库分析KMT2C在胃癌与癌旁的表达差异。采用Western blot检测KMT2C在胃癌与癌旁临床样本中的表达差异。通过Kaplan-Meier Plotter数据库分析KMT2C对胃癌患者预后的影响。采用细胞实验(克隆形成、EdU及CCK-8检测)及皮下瘤负荷模型检测KMT2C在体内外对胃癌细胞增殖能力的影响。结果KMT2C在胃癌中高表达。胃癌患者中KMT2C高表达组相对于KMT2C低表达组预后较差。敲减KMT2C在体内外均有抑制胃癌细胞增殖的作用。基因集富集分析(GSEA)发现KMT2C影响c-Myc信号通路。敲减KMT2C后,H3K4me1蛋白表达水平降低,同时,CDK4的mRNA与蛋白表达水平降低。KMT2C与c-Myc核内结合促进了c-Myc与CDK4的启动子区域的结合。结论KMT2C通过影响c-Myc/CDK4信号通路促进胃癌细胞增殖。

Objective To investigate the role of lysine specific methyltransferase 2C(KMT2C)in the development of gastric cancer and its mechanism.Methods The expression differences of KMT2C in gastric cancer and paraneoplastic tissues were analyzed in TCGA database.Expression levels of KMT2C in gastric cancer tissues and paracancerous tissues were detected by Western blotting.The effect of KMT2C on the prognosis of gastric cancer patients was analyzed by Kaplan-Meier Plotter.Cellular assays(clone formation,EdU and CCK-8 assay)and subcutaneous tumor load model were used to detect the effect of KMT2C on the proliferation ability of gastric cancer cells in vitro and in vivo.Results KMT2C was highly expressed in gastric cancer tissues.The prognosis of patients in KMT2C high expression group was poorer than that of IKMT2C low expression group.Knockdown of KMT2C could inhibit the proliferation of gastric cancer cell both in vitro and in vivo.GSEA analysis revealed that KMT2C had a regulatory effect on c Myc signaling pathway.Knockdown of KMT2C suppressed the expression of H3K4mel protein,while the RNA and protein levels of CDK4 were reduced.Intranuclear binding of KMT2C to c Myc promoted the binding of c-Myc to the promoter region of CDK4.Conclusion K MT2C promotes gastric cancer cell proliferation by regulating c Myc/CDK4 signaling pathway.