Tumor Biology

, Volume 36, Issue 7, pp 5467–5472 | Cite as

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

  • Shuxiang Hu
  • Ruiyang Tao
  • Shouyu Wang
  • Chaoqun Wang
  • Xiankun Zhao
  • Hua Zhao
  • Lijuan Li
  • Shaohua Zhu
  • Yan He
  • Xinghong Jiang
  • Yuzhen Gao
Research Article

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.

Keywords

Hepatocellular carcinoma Hepatocellular carcinoma downregulated 1 miR-21 

Abbreviations

HCC

Hepatocellular carcinoma

HEPN1

Hepatocellular carcinoma, downregulated 1

3′UTR

3′ untranslated region

miR

microRNA

HBV

Hepatitis B virus

HCV

Hepatitis C virus

Notes

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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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Shuxiang Hu
    • 1
  • Ruiyang Tao
    • 1
  • Shouyu Wang
    • 1
  • Chaoqun Wang
    • 1
  • Xiankun Zhao
    • 1
  • Hua Zhao
    • 2
  • Lijuan Li
    • 1
  • Shaohua Zhu
    • 1
  • Yan He
    • 3
  • Xinghong Jiang
    • 4
  • Yuzhen Gao
    • 1
  1. 1.Department of Forensic MedicineMedical College of Soochow UniversitySuzhouChina
  2. 2.Department of General SurgeryThe First Affiliated Hospital of Soochow UniversitySuzhouChina
  3. 3.Department of EpidemiologyMedical College of Soochow UniversitySuzhouChina
  4. 4.Department of Physiology and Neurobiology, Key Laboratory of Pain Research & TherapyMedical College of Soochow UniversitySuzhouChina

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