KMT6在肝癌细胞转移中的作用及对肝癌预后的影响

目的:探讨组蛋白赖氨酸甲基转移酶6(histone lysine methyltransferase 6,KMT6)对人肝癌细胞转移的调控作用及对肝癌患者预后的影响。方法:采用RNA干涉技术合成靶向KMT6的小干扰RNA(KMT6 siRNA)片段,瞬时转染至人肝癌细胞系Huh-7。随后,分别采用细胞黏附实验、细胞侵袭实验以及划痕迁移实验检测肝癌细胞的黏附、侵袭和迁移等肿瘤细胞转移能力。运用Oncomine数据库和cBioportal肝癌数据库分析KMT6的表达情况及对肝癌预后的影响。结果:靶向KMT6的小干扰RNA(KMT6 siRNA)片段瞬时转染至人肝癌细胞系Huh-7后,KMT6蛋白的表达显著下降,且黏附率、侵袭率和划痕修复率均显著降低(P<0.05)。Oncomine肝癌数据库分析表明肝癌组织KMT6的表达增加,cBioportal肝癌数据库分析表明KMT6基因改变与肝癌患者预后不良密切相关。结论:KMT6分子可促进肝癌细胞黏附、侵袭和迁移,其基因改变与肝癌患者预后不良显著相关。KMT6分子有望成为肝癌治疗的新靶点。

Effect of KMT6 on the Metastasis of Hepatocellular Carcinoma Cells and Prognosis of Hepatocellular Carcinoma Patients

ABSTRACT Objective: To investigate the effect of histone lysine methyltransferase 6 (KMT6) on metastasis of hepatocellular carcinoma (HCC) cells and prognosis of HCC patients. Methods: In this study, RNA interference was utilized to transiently downregulate the expression of KMT6 in Huh-7 cells. KMT6 siRNA was then used to investigate the effect of KMT6 on metastasis including adhesion, invasion and migration potentials in Huh-7. Oncomine database and cBioportal database were used to analyze the expression level of KMT6 and its effect on the prognosis of HCC. Results: The expression level of KMT6 protein in Huh-7 cells was significantly decreased after transient transfection of KMT6 siRNA compared to those transfected with the negative control siRNA. The numbers of attached cells, invaded cells and wound closure rate were significantly decreased in KMT6 siRNA transfected Huh-7 cells compared to those transfected with the negative control siRNA (P<0.05). Oncomine database showed that KMT6 expression is increased in HCC tissues. cBioportal database showed that KMT6 gene alteration correlates with poor prognosis of HCC patients. Conclusion: KMT6 can promote adhesion, invasion and migration of HCC cells. KMT6 gene alteration is significantly associated with poor prognosis in HCC patients. KMT6 may be a novel target for HCC treatment.