Su Jing, Wang Qing, Liu Yiping, Zhong Meizuo
Department of Oncology, Xiangya Hospital, Central South University, Xiangya Road 88#, Changsha, 410078, Hunan, People's Republic of China,
Mol Cell Biochem. 2014 Jul;392(1-2):289-96. doi: 10.1007/s11010-014-2039-x. Epub 2014 Mar 27.
The poor prognosis of hepatocellular carcinoma (HCC) is mainly due to the development of invasion and metastasis. Recent data strongly suggests the important role of miRNAs in cancer progression, including invasion and metastasis. Here, we found miR-217 expression was much lower in highly invasive MHCC-97H HCC cells and metastatic HCC tissues. Restored miR-217 expression with miR-217 mimics inhibited invasion of MHCC-97H cells. Inversely, miR-217 inhibition enhanced the invasive ability of Huh7 and MHCC-97L cells. Mechanically, bioinformatics analysis combined with experimental analysis demonstrated E2F3 was a novel direct target of miR-217. Moreover, E2F3 protein level was positively associated with HCC metastasis and functional analysis confirmed the positive role of E2F3 in HCC cell invasion. Our findings suggest miR-217 function as a potential tumor suppressor in HCC progression and miR-217-E2F3 axis may be a novel candidate for developing rational therapeutic strategies.
肝细胞癌（HCC）预后较差，主要是由于其发生侵袭和转移。最近的数据有力地表明了miRNA在癌症进展（包括侵袭和转移）中的重要作用。在此，我们发现miR-217在高侵袭性的MHCC-97H肝癌细胞和转移性肝癌组织中的表达水平要低得多。用miR-217模拟物恢复miR-217的表达可抑制MHCC-97H细胞的侵袭。相反，抑制miR-217可增强Huh7和MHCC-97L细胞的侵袭能力。机制上，生物信息学分析结合实验分析表明E2F3是miR-217的一个新的直接靶点。此外，E2F3蛋白水平与肝癌转移呈正相关，功能分析证实E2F3在肝癌细胞侵袭中起积极作用。我们的研究结果表明，miR-217在肝癌进展中作为一种潜在的肿瘤抑制因子发挥作用，并且miR-217-E2F3轴可能是开发合理治疗策略的一个新的候选靶点。
