Deng Biao, Qu Lei, Li Jinfang, Fang Jiaqing, Yang Shouwen, Cao Zhongwei, Mei Zhechuan, Sun Xing
Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
Department of Neurology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Sci Rep. 2016 May 27;6:26679. doi: 10.1038/srep26679.
Previous studies have shown that the expression of miR-211 was downregulated in hepatocellular carcinoma (HCC). However, the molecular function and mechanism of miR-211 in HCC growth and invasion are largely unclear. We found that miR-211 is downregulated in HCC tissues and cell lines, respectively. Further results showed that low miR-211 associated with TNM stage, vein invasion status, and poor prognosis. Ectopic expression of miR-211 effectively suppressed HCC cell proliferation, migration and invasion both in vitro and in vivo. We identified SPARC as a bona fide target of miR-211, and overexpression of miR-211 decreased the mRNA and protein expression of SPARC. Finally, we confirmed that the overexpression of SPARC in miR-211-expressing HCC cells can partially restore the inhibitory effect of miR-211. Taken together, our results demonstrated that loss of miR-211 expression and thus uncontrolled SPARC overexpression might drive progression of HCC, which may provide a novel therapeutic strategy for the treatment of HCC.
先前的研究表明，miR-211在肝细胞癌（HCC）中的表达下调。然而，miR-211在HCC生长和侵袭中的分子功能及机制在很大程度上尚不清楚。我们发现miR-211分别在HCC组织和细胞系中表达下调。进一步的结果表明，低水平的miR-211与TNM分期、静脉侵犯状态及不良预后相关。miR-211的异位表达在体外和体内均有效抑制HCC细胞的增殖、迁移和侵袭。我们确定SPARC是miR-211真正的靶标，miR-211的过表达降低了SPARC的mRNA和蛋白表达。最后，我们证实，在表达miR-211的HCC细胞中过表达SPARC可部分恢复miR-211的抑制作用。综上所述，我们的结果表明，miR-211表达缺失从而导致SPARC不受控制地过表达可能推动了HCC的进展，这可能为HCC的治疗提供一种新的治疗策略。
