Liu Yahui, Zhang Wei, Liu Kai, Liu Songyang, Ji Bai, Wang Yingchao
Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University Changchun 130021, Jilin Province, China.
Am J Transl Res. 2016 May 15;8(5):2159-68. eCollection 2016.
Accumulating evidence suggests that miR-138 expression was frequently downregulated in different cancer types and involves in the progression of tumorigenesis. However, the biological role and molecular mechanism of miR-138 involvement in hepatocellular carcinoma (HCC) still remains largely unknown. Therefore, in the present study, we investigated the role of miR-138 in the progression of HCC. We found that miR-138 expression levels were significantly downregulated in HCC tissues and cell lines compared with the corresponding noncancerous liver tissues and normal hepatic cell line. In addition, we also found that enforced expression of miR-138 inhibited proliferation, colony formation, migration and invasion in HCC cells. Using a luciferase reporter assay, SOX9 was confirmed as a direct target of miR-138. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay showed that overexpression of miR-138 in HCC cells significantly inhibited SOX9 expression on mRNA level and protein level. Furthermore, SOX9 expression was significantly upregulated in HCC tissues and cell lines, and its mRNA expression is negative correlated with miR-138 expression in clinical HCC tissues (r=-0.689, P<0.01). Of note, downregulation of SOX9 performed similar effects with overexpression of miR-138. These findings suggested that miR-138 functioned as a tumor suppressor in HCC partially via repressing SOX9 expression.
越来越多的证据表明，miR-138在不同癌症类型中表达经常下调，并参与肿瘤发生的进程。然而，miR-138参与肝细胞癌（HCC）的生物学作用和分子机制仍 largely未知。因此，在本研究中，我们研究了miR-138在HCC进程中的作用。我们发现，与相应的癌旁肝组织和正常肝细胞系相比，HCC组织和细胞系中miR-138表达水平显著下调。此外，我们还发现miR-138的强制表达抑制了HCC细胞的增殖、集落形成、迁移和侵袭。通过荧光素酶报告基因检测，证实SOX9是miR-138的直接靶点。定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹分析表明，HCC细胞中miR-138的过表达在mRNA水平和蛋白质水平上显著抑制SOX9表达。此外，SOX9在HCC组织和细胞系中表达显著上调，其mRNA表达与临床HCC组织中miR-138表达呈负相关（r=-0.689，P<0.01）。值得注意的是，SOX9的下调与miR-138的过表达具有相似的作用。这些发现表明，miR-138在HCC中作为肿瘤抑制因子发挥作用，部分是通过抑制SOX9表达实现的。
