MicroRNA-491 is involved in metastasis of hepatocellular carcinoma by inhibitions of matrix metalloproteinase and epithelial to mesenchymal transition

Authors

  • Yun Zhou,

    1. Department of General Surgery, The Second Affiliated Hospital, School of Public Health, Nanjing Medical University, Nanjing, China
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    • Authors contributed equally.
  • Yuan Li,

    1. The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Ch
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    • Authors contributed equally.
  • Jing Ye,

    1. Department of General Surgery, The Second Affiliated Hospital, School of Public Health, Nanjing Medical University, Nanjing, China
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  • Rongrong Jiang,

    1. The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Ch
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  • Han Yan,

    1. The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Ch
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  • Xiaojun Yang,

    1. Department of General Surgery, The Second Affiliated Hospital, School of Public Health, Nanjing Medical University, Nanjing, China
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  • Qizhan Liu,

    1. The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Ch
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  • Jianping Zhang

    Corresponding author
    • Department of General Surgery, The Second Affiliated Hospital, School of Public Health, Nanjing Medical University, Nanjing, China
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Correspondence

Jianping Zhang, Department of General Surgery, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China

Tel: +86 25 5850 9888

Fax: +86 25 5850 9990

e-mail: drjpzhang@hotmail.com

Abstract

Background & Aims

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide; the prognosis of HCC patient remains poor owing to intrahepatic and extrahepatic metastasis and postsurgical recurrence. The aim of the present study is to determine the molecular mechanisms underlying the metastasis of HCC.

Methods

HCC patients and treated HCC cells were molecularly characterized by miRNA microarray analysis, qRT-PCR, Western blots, transwell assay, and immunohistochemistry.

Results

Here, by employing a miRNAs microarray analysis, we found that miR-491 level was the most significant down-regulation in poorly differentiated HCC tissue compared with well-differentiated HCC tissue. We then selected HepG2 (very low migratory capacity), MHCC97L (low migratory capacity) and MHCC97H (high migratory capacity), as well as HCC tissues with different status to further investigate the effects of miR-491 on the metastasis of HCC. Our data showed that miR-491 levels were inversely correlated with different status of differentiation in HCC tissues and with migratory potential in HCC cell lines. In HepG2 cells, inhibition of miR-491 increased the expression of matrix metalloproteinase 2/9 (MMP-2/9) and the migratory potential; however, in MHCC97H cells, overexpression of miR-491 level decreased the expression of MMP-2/9 and the migratory capacity. Moreover, miR-491 had a positive relationship with E-cadherin level; however, it had a negative relationship with vimentin level both in cell lines and tissue samples of HCC. MiR-491 levels of non-metastasis HCC tissue are higher than that of metastasis HCC tissue.

Conclusion

Our results suggest that miR-491 is involved in metastasis of HCC by blocking EMT and decreasing MMP-9 levels, which may provide a new clue for preventing tumour metastasis of HCC.

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