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Downregulation of miR-101-3p by hepatitis B virus promotes proliferation and migration of hepatocellular carcinoma cells by targeting Rab5a

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Abstract

RAB GTPase 5A (RAB5A), a member of the Rab subfamily of small GTPases, acts as an oncogene and has been associated with various key cellular functions, including cell growth, differentiation, apoptosis and angiogenesis. Recently, it has been reported that the Rab5a gene is involved in the progression of cancer. Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers, and it is usually associated with persistent hepatitis B virus (HBV) infections. Emerging evidence suggests that HBV alters microRNA (miRNA) expression profiles, but the mechanisms underlying this process have not yet been fully elucidated. Here, we examine how HBV affects the production of miR-101-1, which has been shown to be downregulated in HCC. We found that HBV could repress miR-101-3p by inhibiting its promoter activity. Downregulation of miR-101-3p promoted cancer cell growth and migration, and a specific miR-101-3p inhibitor was able to enhance proliferation and migration. Moreover, we identified Rab5a was one of the target genes of miR-101-3p in HBV-related HCC. Forced expression of miR-101-3p in liver cell lines resulted in a marked reduction of the expression of Rab5a at both the mRNA and protein level by directly targeting the 3′untranslated region of Rab5a. Overexpression of Rab5a resulted in a reversal of the suppression of proliferation and migration of SMMC-7721 cells mediated by miR-101-3p. Taken together, our data show that HBV can downregulate miR-101-3p expression by inhibiting its promoter activity and that downregulation of miR-101-3p promotes HCC cell proliferation and migration by targeting Rab5a. This provides new insights into the mechanisms of HBV-related HCC pathogenesis.

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Acknowledgments

This work was supported by Nature Science Foundation of China (30771924) and Natural Science Foundation Project of CQ CSTC (2010BB5359).

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Authors and Affiliations

  1. Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, 1 Yi Xue Yuan Road, Chongqing, 400016, China

    Yanrui Sheng, Chengcheng Zou, Sen Wang, Yiyi Cao, Jingnan Zhang, Ailong Huang & Hua Tang

  2. Department of forensic medicine, Chongqing Medical University, Chongqing, 400016, China

    Jianbo Li

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  1. Yanrui Sheng
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  2. Jianbo Li
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  3. Chengcheng Zou
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  4. Sen Wang
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  7. Ailong Huang
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  8. Hua Tang
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Correspondence to Hua Tang.

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Y. Sheng and J. Li contributed equally to this work.

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Sheng, Y., Li, J., Zou, C. et al. Downregulation of miR-101-3p by hepatitis B virus promotes proliferation and migration of hepatocellular carcinoma cells by targeting Rab5a. Arch Virol 159, 2397–2410 (2014). https://doi.org/10.1007/s00705-014-2084-5

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  • DOI: https://doi.org/10.1007/s00705-014-2084-5

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