Prognostic significance of miR-218 in human hepatocellular carcinoma and its role in cell growth

Tu,Kangsheng; Li,Chao; Zheng,Xin; Yang,Wei; Yao,Yingmin; Liu,Qingguang

doi:10.3892/or.2014.3386

Prognostic significance of miR-218 in human hepatocellular carcinoma and its role in cell growth

Authors:
- Kangsheng Tu
- Chao Li
- Xin Zheng
- Wei Yang
- Yingmin Yao
- Qingguang Liu
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Affiliations: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: August 7, 2014 https://doi.org/10.3892/or.2014.3386
Pages: 1571-1577

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Abstract

MicroRNA-218 (miR-218) is considered a tumor suppressor in human cancer. In the present study, miR-218 expression was found to be significantly lower in human hepatocellular carcinoma (HCC) than in normal tumor-adjacent tissues. miR-218 was clearly silenced or downregulated in five HCC cells (HepG2, Hep3B, SMMC-7721, Huh7 and Bel-7402) compared with normal hepatocytes (LO2). The low expression of miR-218 conferred a poor 5-year survival in HCC patients. Multivariate Cox regression analysis indicated that miR-218 was an independent prognostic factor in HCC. Ectopic expression of miR-218 inhibited proliferation and promoted apoptosis in HepG2 and SMMC-7721 cells. In tumor bearing mice, miR-218 slowed down tumor growth by inducing apoptosis and growth arrest. Restoring miR-218 expression resulted in downregulation of B lymphoma Mo-MLV insertion region 1 homolog (BMI-1) mRNA and protein level in HepG2 and SMMC-7721 cells. In addition, BMI-1 mRNA expression in HCC was significantly higher than that in non-cancerous tissues. BMI-1 mRNA was inversely correlated with miR-218 expression in HCC tissues. In conclusion, miR-218 may serve as a prognostic biomarker and induce apoptosis and growth arrest by downregulating BMI-1 in HCC.

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