Dou Changwei, Wang Yufeng, Li Chao, Liu Zhikui, Jia Yuli, Li Qing, Yang Wei, Yao Yingmin, Liu Qingguang, Tu Kangsheng
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Oncotarget. 2015 May 30;6(15):13216-28. doi: 10.18632/oncotarget.3916.
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.
据报道，微小RNA-212（miR-212）在不同的人类恶性肿瘤中发挥致癌或抑癌作用。在此，我们证明肝细胞癌（HCC）组织中miR-212的平均水平显著低于配对的癌旁组织。同样，与未转化的肝细胞系相比，HCC细胞系中miR-212的表达明显降低。miR-212的异位表达抑制了HepG2细胞的活力和增殖，并诱导其凋亡。相反，miR-212的下调增加了Bel-7402细胞的活力和增殖，并抑制了其凋亡。体内研究表明，miR-212通过抑制增殖和诱导凋亡来抑制HCC的肿瘤生长。此外，我们证实叉头框蛋白A1（FOXA1）是miR-212的直接靶点，并且它消除了miR-212在HCC中的功能。最后，我们发现miR-212和FOXA1的异常表达明显与HCC的不良预后特征相关。miR-212、FOXA1及其组合是预测HCC患者生存的有价值的预后标志物。总之，miR-212可能作为HCC患者的预后指标，并至少部分地通过抑制FOXA1发挥肿瘤抑制作用。
