LukS-PV通过下调HDAC3抑制肝癌细胞增殖  

LukS-PV inhibited the proliferation of hepatocellular carcinoma cells by down-regulating HDAC3

作　　者：汪自然 马凡 丁篷生 马筱玲 Wang Ziran;Ma Fan;Ding Pengsheng(Dept of Clinical Laboratory,The Affiliated Provincial Hospital of Anhui Medical University,Hefei 230001)

机构地区：[1]安徽医科大学附属省立医院检验科,合肥230001

出　　处：《安徽医科大学学报》2020年第6期926-931,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81972001)。

摘　　要：目的研究金黄色葡萄球菌杀白细胞素S组分(LukS-PV)对肝癌(HCC)细胞增殖的影响并初步探究其机制。方法不同浓度(0.25、0.5、0.75、1μmol/L)的LukS-PV处理肝癌HepG2和Huh7细胞后,利用CCK-8法评估各组细胞增殖能力。泛乙酰化抗体检测LukS-PV作用后总体乙酰化水平的改变,定量蛋白组学检测LukS-PV作用HepG2细胞后蛋白表达谱的改变。利用TCGA数据库分析组蛋白去乙酰化酶3(HDAC3)在HCC中的表达情况及预后相关性。使用RT-PCR和Western blot验证不同浓度LukS-PV作用HepG2和Huh7细胞后HDAC3 mRNA和蛋白水平的改变。使用特异性SiRNA敲低HDAC3后检测HCC细胞增殖能力的变化。结果 LukS-PV可以降低HCC细胞的增殖能力且呈时间依赖性和浓度依赖性。LukS-PV可以增加HepG2细胞的乙酰化水平,定量蛋白组学结果显示LukS-PV作用HepG2细胞后HDAC3表达下调。TCGA数据分析表明HCC组织中HDAC3 mRNA表达水平高于正常组织,高表达HDAC3的患者生存期低于低表达患者。LukS-PV在HepG2和Huh7细胞株中可以下调HDAC3的mRNA和蛋白水平。敲低HDAC3后可以降低HCC细胞HepG2和Huh7细胞的增殖能力。结论 LukS-PV可能通过下调HDAC3的表达抑制HCC细胞的增殖,为HCC的精准靶向治疗提供了新的研究思路。Objective To study the effect of S component of panton-valentine leucocidin(LukS-PV)on proliferation of hepatocellular carcinoma(HCC)cells and its mechanism.Methods HepG2 and Huh7 cells were treated with LukS-PV at different concentrations(0.25,0.5,0.75,1μmol/L).Cell proliferation was evaluated by CCK-8 method.Changes in overall acetylation level after LukS-PV treatment were detected by pan-acetylated antibody,and changes in protein expression profile of HepG2 cells after LukS-PV treatment were detected by quantitative proteomics.TCGA database was used to analyze the expression of histone deacetylase 3(HDAC3)in HCC and its prognostic correlation.RT-PCR and Western blot were used to verify the changes of HDAC3 mRNA and protein levels in HepG2 and Huh7 cells treated with different concentrations of LukS-PV.Changes in proliferation capacity of HCC cells were detected after HDAC3 knockdown with specific SiRNA.Results LukS-PV could decrease the proliferation ability of HCC cells in a time-dependent and concentration-dependent manner.LukS-PV could increase the acetylation level of HepG2 cells,and quantitative proteomics results showed that HDAC3 expression was down-regulated in HepG2 cells after LukS-PV treatment.TCGA data analysis showed that the expression level of HDAC3 mRNA in liver cancer tissues was higher than that in normal tissues,and the survival time of patients with high HDAC3 expression was lower than that of patients with low HDAC3 expression.The mRNA and protein levels of HDAC3 were down-regulated by LukS-PV in HepG2 and Huh7 cell lines.Knockdown of HDAC3 reduced the proliferation of HepG2 and Huh7 cells.Conclusion LukS-PV may inhibit the proliferation of HCC cells by down-regulating the expression of HDAC3,which provides a new research idea for the precise and targeted treatment of HCC.

关 键 词：杀白细胞素 肝细胞癌 组蛋白去乙酰化酶3 

分 类 号：R735.7[医药卫生—肿瘤]