MiR-570 inhibited the cell proliferation and invasion through directly targeting B7-H1 in hepatocellular carcinoma
MiR-570 inhibited the cell proliferation and invasion through directly targeting B7-H1 in hepatocellular carcinoma
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MiR-570直接靶向B7-H1抑制肝细胞癌细胞增殖和侵袭
DOI：
10.1007/s13277-015-3644-3
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发表时间：
2015-11-01
期刊：
影响因子：
--
通讯作者：
Wang, Changjun
中科院分区：
文献类型：
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作者：
Guo, Wei;Tan, Wei;Wang, Changjun
最近的一项研究报道，miR-570是酒精性肝病microRNA基因网络中最重要的microRNA，有可能进展为肝细胞癌。然而，关于miR-570在肝细胞癌进展中的表达和特异性功能，特别是miR-570发挥其功能并调节肝细胞癌细胞恶性表型的分子机制，知之甚少。在此，我们观察到miR-570在肝细胞癌细胞系（Bel-7404、Huh-7和HepG 2）中高表达，而B7-H1与非恶性细胞系（L-02和HL-7702）相比低表达。转染miR-570模拟或敲低B-H1可抑制B7-H1的表达，从而促进细胞凋亡，抑制细胞增殖和侵袭。使用双荧光素酶报告系统，我们验证了B7-H1是miR-570的直接靶点。B7-H1的过表达逆转了miR-570对增殖和侵袭的抑制作用。此外，miR-570抑制体内致瘤性。因此，我们的观察证实了miR-570通过直接靶向肝癌细胞中的B7-H1而在肝癌细胞中起增殖和转移抑制剂的作用，合理地提出了miR-570有可能成为人类肝癌的有用的临床无创诊断或预测标志物。
A recent study reported that miR-570 was the most important microRNA in the microRNA gene networks of alcoholic liver disease that has the potential of progressing to hepatocellular carcinoma. However, litter is known regarding the expression and specific function of miR-570 in the progression of hepatocellular carcinoma, especially its molecular mechanisms by which miR-570 exerts its functions and modulates the malignant phenotypes of hepatocellular carcinoma cells. Here, we observed that miR-570 was highly expressed in hepatocellular carcinoma cell lines (Bel-7404, Huh-7, and HepG2), while B7-H1 was lowly expressed, compared to nonmalignant cell line (L-02 and HL-7702). Transfection of miR-570 mimics or knockdown of B-H1 suppressed the expression of B7-H1, which promotes cell apoptosis and inhibits the cell proliferation and invasion. Using a dual-luciferase reporter system, we verified that B7-H1 is a direct target of miR-570. The overexpression of B7-H1 reversed the inhibition of proliferation and invasion by miR-570. In addition, miR-570 suppressed tumorigenicity in vivo. Hence, our observation confirmed that miR-570 works as proliferation and metastatic suppressor in hepatocellular carcinoma cells through directly targeting B7-H1 in hepatocellular carcinoma cell and rationally presents that miR-570 has the potential to be a useful clinical noninvasive diagnostics or predictive marker in human hepatocellular carcinoma.