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微小RNA-608作为一种预后标志物,通过巨噬细胞移动抑制因子抑制肝细胞癌的细胞增殖。

MicroRNA-608 acts as a prognostic marker and inhibits the cell proliferation in hepatocellular carcinoma by macrophage migration inhibitory factor.

作者信息

Wang Kejia, Liang Qing, Wei Li, Zhang Wei, Zhu Ping

机构信息

Department of Pathology, No. 401 Hospital of PLA, 22 Minjiang Road, Qingdao, 266071, China.

Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, 200032, China.

出版信息

Tumour Biol. 2016 Mar;37(3):3823-30. doi: 10.1007/s13277-015-4213-5. Epub 2015 Oct 16.

Abstract

Human hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the world. Research on HCC has recently focused on microRNAs (miRNAs) that play crucial roles in cancer development and progression of HCC. In this study, we aimed to analyze the expression and function of a metastasis-associated microRNA-608 (miR-608) in HCC. Samples of human HCC and matched adjacent normal tissues were surgically removed, and miR-608 expression and the pathological characteristics of HCC were investigated. In this study, we found that miR-608 expression was significantly reduced in HCC and its expression levels were highly associated with tumor size, differentiation, clinical stage, and overall and disease-free survival of HCC. Overexpression of miR-608 in HCC cell lines HepG2 and SK-Hep-1 inhibited cell proliferation by G1 arrest. Macrophage migration inhibitory factor (MIF), a potential target gene of miR-608, was inversely correlated with miR-608 expression in HCC tissues and cell lines. Furthermore, we demonstrated that MIF was directly regulated by miR-608 and the restoration of MIF expression reversed the inhibitory effects of miR-608 on HCC cell proliferation. Taken together, these findings collectively demonstrate that miR-608 exerts its anti-cancer function by directly targeting MIF in HCC, indicating a potential novel prognostic biomarker and therapeutic target for HCC.

摘要

人类肝细胞癌(HCC)是世界上最常见的恶性肿瘤之一。近年来,对HCC的研究集中在微小RNA(miRNA)上,这些miRNA在HCC的癌症发生和发展中起着关键作用。在本研究中,我们旨在分析一种转移相关的微小RNA-608(miR-608)在HCC中的表达及功能。手术切除人HCC样本及配对的癌旁正常组织,研究miR-608的表达及HCC的病理特征。在本研究中,我们发现miR-608在HCC中的表达显著降低,其表达水平与肿瘤大小、分化程度、临床分期以及HCC患者的总生存期和无病生存期高度相关。在HCC细胞系HepG2和SK-Hep-1中过表达miR-608可通过使细胞停滞于G1期来抑制细胞增殖。巨噬细胞移动抑制因子(MIF)是miR-608的一个潜在靶基因,其在HCC组织和细胞系中的表达与miR-608呈负相关。此外,我们证实MIF直接受miR-608调控,恢复MIF表达可逆转miR-608对HCC细胞增殖的抑制作用。综上所述,这些发现共同表明miR-608在HCC中通过直接靶向MIF发挥其抗癌功能,这表明miR-608可能是一种新型的HCC预后生物标志物和治疗靶点。

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