MicroRNA-212 suppresses tumor growth of human hepatocellular carcinoma by targeting FOXA1.
MicroRNA-212 suppresses tumor growth of human hepatocellular carcinoma by targeting FOXA1.
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MicroRNA-212通过靶向FOXA1抑制人肝细胞癌的肿瘤生长
DOI：
10.18632/oncotarget.3916
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发表时间：
2015-05-30
期刊：
影响因子：
--
通讯作者：
Tu K
中科院分区：
文献类型：
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作者：
Dou C;Wang Y;Li C;Liu Z;Jia Y;Li Q;Yang W;Yao Y;Liu Q;Tu K
MicroRNA-212（miR-212）在多种人类恶性肿瘤中具有致癌或抑瘤作用。在这里，我们证明了miR-212在肝细胞癌（HCC）组织中的平均水平显著低于匹配的肿瘤相邻组织。同样，与未转化的肝细胞系相比，miR-212在HCC细胞系中的表达明显降低。miR-212的异位表达可抑制HepG 2细胞的活力和增殖，并诱导细胞凋亡。相反，下调miR-212可增加Bel-7402细胞的存活率和增殖，并抑制细胞凋亡。体内研究表明，miR-212通过抑制细胞增殖和诱导细胞凋亡抑制肝癌的生长。此外，我们证实叉头盒蛋白A1（FOXA 1）是miR-212的直接靶点，它在HCC中消除了miR-212的功能。最后，我们发现miR-212和FOXA 1的异常表达与HCC的不良预后特征明显相关。miR-212、FOXA 1及其联合应用是预测HCC患者生存的有价值的预后指标。总之，miR-212可作为HCC患者的预后指标，并至少部分通过抑制FOXA 1发挥肿瘤抑制作用。
MicroRNA-212 (miR-212) has been reported to play oncogenic or tumor suppressive role in different human malignancies. Here, we demonstrated that the mean level of miR-212 in hepatocellular carcinoma (HCC) tissues was significantly lower than that in matched tumor-adjacent tissues. Similarly, the expression of miR-212 was obviously reduced in HCC cell lines as compared with a nontransformed hepatic cell line. Ectopic expression of miR-212 inhibited cell viability and proliferation, and induced apoptosis in HepG2 cells. In contrast, down-regulation of miR-212 increased cell viability and proliferation, and suppressed apoptosis in Bel-7402 cells. In vivo studies showed that miR-212 inhibited tumor growth of HCC via suppressing proliferation and inducing apoptosis. Furthermore, we confirmed that Forkhead box protein A1 (FOXA1) was a direct target of miR-212, and it abrogated the function of miR-212 in HCC. Finally, we disclosed that the aberrant expression of miR-212 and FOXA1 was evidently correlated with poor prognostic features of HCC. MiR-212, FOXA1 and their combination were valuable prognostic markers for predicting survival of HCC patients. In conclusion, miR-212 may serve as a prognostic indicator for HCC patients and exerts tumor suppressive role, at least in part, by inhibiting FOXA1.