Song Jianjun, Wang Qi, Luo Yongyun, Yuan Peng, Tang Chaofeng, Hui Yongfeng, Wang Zuozheng
Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University Yinchuan 750004, PR China.
Int J Clin Exp Pathol. 2015 Oct 1;8(10):12728-37. eCollection 2015.
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.
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。