Liu Zhenyu, Wang Jingjie, Mao Yuqing, Zou Bing, Fan Xiaoming
Department of Gastroenterology and Hepatology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China; Department of Gastroenterology and Hepatology, Shenzhen Hospital, Peking University, Shenzhen, Guangdong 518036, P.R. China.
Department of Gastroenterology and Hepatology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China.
Oncol Lett. 2016 Jan;11(1):433-438. doi: 10.3892/ol.2015.3832. Epub 2015 Oct 27.
MicroRNAs (miRNAs) are a class of non-coding RNAs 18-25 nucleotides in length, which play important roles in the regulation of cancer progression through gene silencing. miRNA (miR)-101 has been suggested to be associated with hepatocellular carcinoma (HCC). However, the detailed role of miR-101 in HCC metastasis and the underlying mechanism remain largely unclear. The present study demonstrated that the expression of miR-101 was significantly reduced in HCC tissues compared with that in matched normal adjacent tissues. miR-101 was also found to be downregulated in four HCC cell lines compared with its expression in a normal liver cell line. Vascular endothelial growth factor (VEGF)-C was further identified as a direct target of miR-101, and the protein expression of VEGF-C was downregulated by miR-101 in HepG2 HCC cells. Furthermore, the overexpression of miR-101 and the knockdown of VEGF-C significantly inhibited HepG2 cell migration and invasion, while restoration of VEGF-C reversed the inhibitory effect of miR-101 overexpression on HepG2 cell migration and invasion. Finally, the expression of VEGF-C was notably increased in HCC tissues and cell lines. These findings suggest that miR-101 exerts a suppressive effect on HCC cell migration and invasion, at least in part through the direct inhibition of VEGF-C protein expression. Therefore, the miR-101/VEGF-C axis may serve as a potential therapeutic target for HCC metastasis.
微小RNA（miRNA）是一类长度为18 - 25个核苷酸的非编码RNA，其通过基因沉默在癌症进展调控中发挥重要作用。已有研究表明miRNA（miR）-101与肝细胞癌（HCC）相关。然而，miR-101在HCC转移中的具体作用及潜在机制仍 largely不清楚。本研究表明，与配对的正常相邻组织相比，HCC组织中miR-101的表达显著降低。与正常肝细胞系中的表达相比，在四种HCC细胞系中也发现miR-101表达下调。血管内皮生长因子（VEGF）-C被进一步鉴定为miR-101的直接靶点，在HepG2 HCC细胞中，miR-101下调了VEGF-C的蛋白表达。此外，miR-101的过表达和VEGF-C的敲低显著抑制了HepG2细胞的迁移和侵袭，而VEGF-C的恢复逆转了miR-101过表达对HepG2细胞迁移和侵袭的抑制作用。最后，HCC组织和细胞系中VEGF-C的表达显著增加。这些发现表明，miR-101至少部分通过直接抑制VEGF-C蛋白表达对HCC细胞的迁移和侵袭发挥抑制作用。因此，miR-101/VEGF-C轴可能成为HCC转移的潜在治疗靶点。
