MicroRNA-212 suppresses tumor growth of human hepatocellular carcinoma by targeting FOXA1
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Changwei Dou1, Yufeng Wang1, Chao Li1, Zhikui Liu1, Yuli Jia1, Qing Li1, Wei Yang1, Yingmin Yao1, Qingguang Liu1 and Kangsheng Tu1
1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Kangsheng Tu, email:
Qingguang Liu, email:
Keywords: MiR-212, FOXA1, hepatocellular carcinoma, proliferation, apoptosis
Received: February 02, 2015 Accepted: March 31, 2015 Published: April 23, 2015
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.
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