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微小RNA-34c-3p通过靶向肌动蛋白结合蛋白抑制肝癌细胞的增殖、迁移和侵袭。

miR-34c-3p inhibits cell proliferation, migration and invasion of hepatocellular carcinoma by targeting MARCKS.

作者信息

Song Jianjun, Wang Qi, Luo Yongyun, Yuan Peng, Tang Chaofeng, Hui Yongfeng, Wang Zuozheng

机构信息

Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University Yinchuan 750004, PR China.

出版信息

Int J Clin Exp Pathol. 2015 Oct 1;8(10):12728-37. eCollection 2015.

Abstract

Recent studies have shown that microRNA-34c-3p (miR-34c-3p) is down-regulated in various types of cancers and involved in tumor growth, invasion and metastasis. However, the roles of miR-34c-3p in hepatocellular carcinoma (HCC) are poorly understood. In this study, the expression profile of miR-34c-3pin HCC tissues and cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The correlations of miR-34c-3p expression and clinicopathological characteristics were analyzed. The biological role of MiR-34c-3pin cell proliferation, migration and invasion was examined. In addition, the targets of miR-34c-3p were identified. The results showed that miR-34c-3p expression was significantly down-regulated in HCC tissues and cell lines; low expression level of miR-34c-3p was correlated with vascular invasion and advanced TNM stage. In vitro functional assays showed that overexpression of miR-34c-3pin HepG2 and Huh7 cells significantly reduced cell proliferation, migration and invasion. Furthermore, target analysis and luciferase assay identified myristoylated alanine-rich protein kinase c substrate (MARCKS) as a specific target of miR-34c-3p. Knockdown of MARCKS in HepG2 cells reduced cell migration and invasion, but not cell proliferation. Taken together, our findings implicate the potential application of miR-34c-3p as a tumor suppressor in cancer therapy.

摘要

近期研究表明,微小RNA-34c-3p(miR-34c-3p)在多种癌症中表达下调,并参与肿瘤生长、侵袭和转移。然而,miR-34c-3p在肝细胞癌(HCC)中的作用尚不清楚。在本研究中,通过定量实时聚合酶链反应(qRT-PCR)检测了miR-34c-3p在HCC组织和细胞系中的表达谱。分析了miR-34c-3p表达与临床病理特征的相关性。研究了miR-34c-3p在细胞增殖、迁移和侵袭中的生物学作用。此外,还鉴定了miR-34c-3p的靶标。结果显示,miR-34c-3p在HCC组织和细胞系中表达显著下调;miR-34c-3p低表达水平与血管侵犯和TNM分期进展相关。体外功能实验表明,在HepG2和Huh7细胞中过表达miR-34c-3p可显著降低细胞增殖、迁移和侵袭。此外,靶标分析和荧光素酶实验确定肉豆蔻酰化富含丙氨酸的蛋白激酶C底物(MARCKS)是miR-34c-3p的特异性靶标。在HepG2细胞中敲低MARCKS可降低细胞迁移和侵袭,但不影响细胞增殖。综上所述,我们的研究结果表明miR-34c-3p作为一种肿瘤抑制因子在癌症治疗中具有潜在应用价值。

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