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MicroRNA-21 promotes cell proliferation in human hepatocellular carcinoma partly by targeting HEPN1

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Tumor Biology

Abstract

It has been reported that miR-21 is upregulated in hepatocellular carcinoma (HCC), and overexpressed miR-21 plays a key role in promoting cell cycle progression, reducing cell death and favoring angiogenesis and invasion. Overexpression of hepatocellular carcinoma, downregulated 1 (HEPN1) exhibits an antiproliferative effect on HepG2 cells, suggesting that silencing of HEPN1 may contribute to carcinogenesis of hepatocytes. In silico analysis revealed that HEPN1 may be a potential target of miR-21. Using quantitative reverse transcription PCR and Western blot, we found that HEPN1 was strikingly downregulated in both mRNA (fold change was 33.5, P < 0.0001) and protein levels in human HCC tumor tissues, in comparison with the adjacent non-tumor tissues. More importantly, the expression level of HEPN1 was inversely correlated with the expression of miR-21 in HCC (R 2 = 0.442, P < 0.0001). The combination between the 3′ untranslated region (UTR) of HEPN1 with miR-21 was experimentally verified by a miRNA luciferase reporter approach. The suppressed cell proliferation upon stimulation of miR-21 inhibitor could be partially abolished by knocking down HEPN1, so inhibition of miR-21 expression in HCC cells profoundly suppressed cell proliferation partially by upregulating HEPN1 expression. Taken together, the current study suggested an underlying mechanism that miR-21 directly target HEPN1 and inhibit its expression during the carcinogenesis of HCC. HEPN1 may thus be a candidate as a therapeutic target for patients with HCC.

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Abbreviations

HCC:

Hepatocellular carcinoma

HEPN1:

Hepatocellular carcinoma, downregulated 1

3′UTR:

3′ untranslated region

miR:

microRNA

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

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Acknowledgments

This study is supported by grants from the National Natural Science Foundation of China (No. 81171893, Nos. 81201574 and 81172898) and Priority Academic Program Development of Jiangsu Higher Education Institutions.

Conflicts of interest

None.

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    Authors and Affiliations

    1. Department of Forensic Medicine, Medical College of Soochow University, Suzhou, 215123, Jiangsu, China

      Shuxiang Hu, Ruiyang Tao, Shouyu Wang, Chaoqun Wang, Xiankun Zhao, Lijuan Li, Shaohua Zhu & Yuzhen Gao

    2. Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China

      Hua Zhao

    3. Department of Epidemiology, Medical College of Soochow University, Suzhou, 215123, Jiangsu, China

      Yan He

    4. Department of Physiology and Neurobiology, Key Laboratory of Pain Research & Therapy, Medical College of Soochow University, Suzhou, 215123, Jiangsu, China

      Xinghong Jiang

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    1. Shuxiang Hu
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    Correspondence to Xinghong Jiang or Yuzhen Gao.

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    Shuxiang Hu, Ruiyang Tao and Shouyu Wang contributed equally to this work.

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    Hu, S., Tao, R., Wang, S. et al. MicroRNA-21 promotes cell proliferation in human hepatocellular carcinoma partly by targeting HEPN1. Tumor Biol. 36, 5467–5472 (2015). https://doi.org/10.1007/s13277-015-3213-9

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    • DOI: https://doi.org/10.1007/s13277-015-3213-9

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