miR-139靶向调控CTAG2对肝癌细胞增殖的影响  

Effects of miR-139 on the proliferation of hepatocellular carcinoma cells by targeting and regulating CTAG2

作　　者：刘巾玮 贾婉莹 臧国杰 王健[3] Liu Jinwei;Jia Wanying;Zang Guojie;Wang Jian(Department of Pharmacy,Chifeng Municipal Hospital,Chifeng,Inner Mongolia 024000,China;School of Phar-macy,Inner Mongolia Medical University,Hohhot,Inner Mongolia 010107,China;Department of Pharmacy Sup-plement,Chifeng Municipal Hospital,Chifeng,Inner Mongolia024000,China)

机构地区：[1]赤峰市医院药剂科,内蒙古自治区赤峰024000 [2]内蒙古医科大学药学院,内蒙古自治区呼和浩特010107 [3]赤峰市医院药供科,内蒙古自治区赤峰024000

出　　处：《中国药物与临床》2024年第23期1506-1511,I0001,I0002,共8页Chinese Remedies & Clinics

基　　金：内蒙古自治区自然科学基金项目(2021BS08021)。

摘　　要：目的探讨miRNA在肝细胞肝癌(HCC)中的表达以及对于细胞增殖的影响,筛选新型HCC特异性治疗靶点,为肝癌新型治疗药物的开发提供理论依据。方法利用edgeR对癌症基因组图谱(TCGA)数据库中HCC组织样本的miRNA表达数据进行差异表达分析,同时进行临床病理参数分析以及靶点预测。进行聚合酶链反应(PCR)检测HCC患者肿瘤及癌旁组织中miR-139的表达,然后通过细胞增殖和细胞毒性(CCK8)检测miR-139-5p mimic、mimic NC、miR-139-5p inhibitor以及inhibitor NC 4组肝癌细胞的增殖活性。结果Pearson相关性分析显示靶基因CTAG2的表达与miR-139-3p和miR-139-5p的表达呈负相关(P<0.05)。miR-139与肿瘤分级低分化(P<0.001)、初始治疗后肿瘤的复发(P<0.05)、T分期Ⅱ~Ⅳ期(P<0.01)以及肿瘤分期Ⅱ~Ⅳ期(P<0.01)呈负相关。PCR检测结果显示与癌旁组织相比,肿瘤组织中的miR-139-5p表达下调。与mimic NC、miR-139-5p inhibitor以及inhibitor NC组相比,miR-139-5p mimic组的miR-139-5p表达增加(P<0.05);通过CCK8检测证明miR-139-5p mimic组的细胞增殖活性低于其余3组。结论miR-139的低表达与靶基因CTAG2的表达均与肝细胞癌的不良预后相关,且miR-139-5p高表达对肝癌细胞增殖具有抑制作用。Objective To investigate the expression of miRNAs in hepatocellular carcinoma(HCC)and their effects on cell proliferation,so as to screen out novel HCC-specific therapeutic targets and provide a theoreti-cal basis for the development of novel therapeutic drugs for HCC.Methods Differential expression analysis of miRNA expression data of HCC tissue samples in TCGA database was performed by edgeR,and clinicopathologi-cal parameter analysis and target prediction were also performed.PCR were performed to detect the expression of miR-139 in the tumors and paracancerous tissues of HCC patients,and then the proliferative activities of hepato-cellular carcinoma cells in the four groups of miR-139-5p mimic,mimic NC,miR-139-5p inhibitor,and inhibitor NC were detected by CCK8.Results The expression of the target gene CTAG2 was negatively correlated with the expression of miR-139-3p and miR-139-5p(P<0.05).miR-139 was correlated with Grade hypo-differentiation(P<0.001),recurrence of tumors after the initial treatment(P<0.05),T-stageⅡ~Ⅳ(P<0.01)and StageⅡ~Ⅳ(P<0.01)were significantly negatively correlated.PCR assay,the results showed that the expression of miR-139-5p was sig-nificantly down-regulated in tumor tissues compared with paracancerous tissues.Compared with the mimic NC,miR-139-5p inhibitor,and inhibitor NC groups,miR-139-5p expression in the miR-139-5p mimic group was signif-icantly increased(P<0.05);the cell proliferation activity of the miR-139-5p mimic group was proved to be signifi-cantly lower than that of the remaining three groups by CCK8 assay. Conclusion The low expression of miR-139 and the expression of the target gene CTAG2 are both associated with poor prognosis in HCC, and the high ex-pression of miR-139-5p has an inhibitory effect on the proliferation of hepatocellular carcinoma cells.

关 键 词：微RNAS 肝肿瘤 细胞增殖 CTAG2 

分 类 号：R735.7[医药卫生—肿瘤]