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微小RNA-708通过靶向SMAD3在肝细胞癌中发挥肿瘤抑制作用。

miRNA-708 functions as a tumour suppressor in hepatocellular carcinoma by targeting SMAD3.

作者信息

Li Qi, Li Sheng, Wu Yaolu, Gao Feng

机构信息

Department of Hepatobiliary Surgery, Yan'an City People's Hospital Yanan, Shaanxi 716000, P.R. China.

The Second Department of General Surgery, Yulin Second Hospital, Yulin Shaanxi 719000, P.R. China.

出版信息

Oncol Lett. 2017 Aug;14(2):2552-2558. doi: 10.3892/ol.2017.6429. Epub 2017 Jun 20.

Abstract

Hepatocellular carcinoma (HCC) is the most frequent subtype of primary liver cancer and the third most common cause of cancer-associated mortality worldwide. Previous studies have reported that microRNAs (miRNAs) serve key roles in the carcinogenesis and progression of HCC by regulating gene expression. The present study investigated the expression patterns, biological roles and underlying mechanisms of miRNA-708 (miR-708) in HCC. The expression levels of miR-708 in HCC tissue samples and cell lines were examined. Cell proliferation, migration and invasion assays were used to evaluate the effect of miR-708 on HCC cells. In addition, bioinformatic and western blotting analyses, and dual luciferase reporter assays were performed to investigate the direct gene target of miR-708. The results of the present study demonstrated that miR-708 expression was significantly decreased in HCC tissue samples and cell lines. In addition, the expression level of miR-708 was associated with increased HCC tumour stage. Furthermore, ectopic expression of miR-708 suppressed HCC cell proliferation, migration and invasion. The results of the present study also indicated that miR-708 targets SMAD family member 3 directly . The results of the present study indicated that miR-708 may be a novel target for future HCC therapy.

摘要

肝细胞癌(HCC)是原发性肝癌最常见的亚型,也是全球癌症相关死亡的第三大常见原因。先前的研究报道,微小RNA(miRNA)通过调节基因表达在HCC的发生和发展中起关键作用。本研究调查了miRNA-708(miR-708)在HCC中的表达模式、生物学作用及潜在机制。检测了miR-708在HCC组织样本和细胞系中的表达水平。采用细胞增殖、迁移和侵袭实验评估miR-708对HCC细胞的影响。此外,进行了生物信息学和蛋白质印迹分析以及双荧光素酶报告基因实验,以研究miR-708的直接基因靶点。本研究结果表明,miR-708在HCC组织样本和细胞系中的表达显著降低。此外,miR-708的表达水平与HCC肿瘤分期增加有关。此外,miR-708的异位表达抑制了HCC细胞的增殖、迁移和侵袭。本研究结果还表明,miR-708直接靶向SMAD家族成员3。本研究结果表明,miR-708可能是未来HCC治疗的新靶点。

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