KMT5A对肝细胞癌迁移侵袭的影响及分子机制研究  

Effects of KMT5A on cell migration and invasion in human hepatocellular carcinoma and its mechanisms

作　　者：李超[1] 刘志奎[1] 窦常伟[1] 涂康生[1] 杨威[1] 

机构地区：[1]西安交通大学第一附属医院肝胆外科,西安市710061

出　　处：《实用医学杂志》2017年第16期2634-2638,共5页The Journal of Practical Medicine

基　　金：陕西省自然科学基础研究计划青年人才项目(编号:2016JQ8047)

摘　　要：目的探讨赖氨酸甲基转移酶5A(lysine methyltransferase 5A,KMT5A)对肝细胞癌(hepato-cellular carcinoma,HCC)迁移及侵袭的影响及潜在分子调控机制。方法免疫组化染色检测60例HCC及癌旁组织中KMT5A的表达情况。siRNA沉默SMMC-7721细胞内KMT5A的表达后分别采用划痕愈合试验及Transwell小室研究细胞迁移及侵袭能力的变化,蛋白质免疫印迹检测细胞内MMP-2蛋白的表达变化。采用miR-186模拟物转染SMMC-7721细胞,qRT-PCR检测过表达miR-186后细胞内KMT5AmRNA的表达变化。结果 HCC组织内高表达的KMT5A蛋白(P=0.038)与肿瘤直径增大(>5 cm,P=0.047)及较晚的TNM分期(Ⅲ+Ⅳ期,P=0.035)相关;沉默KMT5A表达能通过下调MMP-2表达水平而显著抑制肝癌细胞迁移(P=0.031)及侵袭(P=0.010)能力。过表达miR-186能够显著降低肝癌细胞内KMT5A mRNA的表达水平(P=0.007)。结论肝癌中异常高表达的KMT5A与肝癌不良临床病理特征相关。沉默SMMC-7721细胞内KMT5A表达能够显著抑制肝癌细胞迁移和侵袭。Objective To investigate the clinical roles of lysine methyltransferase 5A（KMT5A）in human hepatocellular carcinoma（HCC）and its functions in cell migration and invasion.Methods The expression levels of KMT5A of 60 cases were detected by immunohistochemistry（IHC）.KMT5A siRNA was used to down-regulate the expression of KMT5A in SMMC-7721 cells.Cell migration and invasion were measured by wound healing assays and transwell assays,respectively.Immunoblotting was used to detect the expression of MMP-2 after siRNA transfection.mi R-186 mimics were transfected into SMMC-7721 cells and the mRNA levels of KMT5A was detected by qRT-PCR after transfection.Results High expression of KMT5A was associated with large tumor diameter（5 cm,P=0.047）and advanced TNM stage（Ⅲ＋Ⅳ,P=0.035）.The expression of KMT5A was knocked down by siRNA in SMMC-7721 cells.Down-regulation of KMT5A suppressed cell migration（P=0.031,P=0.006）and invasion（P=0.010）,and impaired MMP-2 expression（P=0.040）.Overexpression of miR-186 could significantly inhibit the expression of KMT5A（P=0.007）.Conclusions Over-expression of KMT5A in HCC tissues associates with poor clinical features.KMT5A knockdown inhibits the migration and invasion on HCC cells.

关 键 词：组蛋白赖氨酸甲基转移酶5A 肝细胞癌 迁移 侵袭 

分 类 号：R735.7[医药卫生—肿瘤]