MicroRNA-639 is Down-Regulated in Hepatocellular Carcinoma Tumor Tissue and Inhibits Proliferation and Migration of Human Hepatocellular Carcinoma Cells Through the KAT7/Wnt/β-Catenin Pathway
MicroRNA-639 is Down-Regulated in Hepatocellular Carcinoma Tumor Tissue and Inhibits Proliferation and Migration of Human Hepatocellular Carcinoma Cells Through the KAT7/Wnt/β-Catenin Pathway
复制标题
DOI：
10.12659/msm.919241
复制
发表时间：
2020-01-19
影响因子：
3.1
通讯作者：
Lu, Jianfeng
中科院分区：
文献类型：
--
作者：
Bai, Zhijie;Xia, Xiaopu;Lu, Jianfeng
背景资料：本研究旨在研究microRNA-639（miR-639）在肝细胞癌（HCC）患者肿瘤组织中的表达及其对患者预后的影响，利用生物信息学和荧光素酶报告基因分析确定miR-639的靶点，以及miR-639在体外人HCC细胞中的作用，以确定所涉及的分子通路。材料/方法：比较了50例HCC患者肿瘤组织和邻近正常肝组织中miR-639的表达水平，Kaplan-Meier曲线确定了与总生存期（OS）的相关性。使用定量逆转录-聚合酶链反应（RT-qPCR）和Western印迹法测定体外培养的HCC细胞中miR-639的表达。采用MTT法、殖民地法和transwell法对肝癌细胞进行研究。结果：miR-639在肝癌组织中的表达明显低于癌旁正常肝组织，并抑制肝癌细胞的增殖和上皮间质转化（EMT）。生物信息学和荧光素酶报告基因分析表明，miR-639直接靶向KAT 7并抑制其表达。KAT 7的表达促进了体外人HCC细胞的增殖和迁移，miR-639通过下调KAT 7/Wnt/beta-catenin信号通路抑制细胞增殖和EMT。miR-639在HCC肿瘤组织中下调，通过下调KAT 7/Wnt/β-这些发现支持miR-639作为肿瘤抑制因子的潜在作用。
Background: This study aimed to investigate the expression of microRNA-639 (miR-639) in tumor tissue from patients with hepatocellular carcinoma (HCC) and its effects on patient outcome, to identify the targets for miR-639 using bioinformatics and luciferase reporter analysis, and the effects of miR-639 in human HCC cells in vitro to identify the molecular pathways involved.Material/Methods: Expression levels of miR-639 were compared in tumor tissue and adjacent normal liver tissue from 50 patients with HCC, and Kaplan-Meier curves identified the association with overall survival (OS). miR-639 expression was measured in HCC cells cultured in vitro using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot. HCC cells were studied using the MTT assay, the colony formation assay, and the transwell assay. Bioinformatics and luciferase reporter analysis identified the role of the histone acetyltransferase gene, KAT7, in HCC.Results: The expression of miR-639 was significantly reduced in HCC tissues compared with normal adjacent liver tissues, and inhibited cell proliferation and epithelial-mesenchymal transition (EMT) of HCC cells. Bioinformatics and luciferase reporter analysis showed that miR-639 directly targeted KAT7 and inhibit its expression. KAT7 expression promoted cell proliferation, and migration of human HCC cells in vitro, and miR-639 inhibited cell proliferation and EMT by down-regulating the KAT7/Wnt/beta-catenin signaling pathway.Conclusions: miR-639 was down-regulated in HCC tumor tissue, and inhibited proliferation and migration of HCC cells by the down-regulation of KAT7/Wnt/beta-catenin signaling and was associated with reduced OS. These findings supported the potential role of miR-639 as a tumor suppressor.