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Tumor Biology

, Volume 37, Issue 4, pp 5039–5047 | Cite as

A c-Myc/miR-17-5p feedback loop regulates metastasis and invasion of hepatocellular carcinoma

  • Dongli Liu
  • Lili Dong
  • Yang Liu
  • Duo Wen
  • Dongmei Gao
  • Huichuan Sun
  • Jia Fan
  • Weizhong Wu
Original Article

Abstract

The molecular mechanisms that control metastasis of hepatocellular cancer (HCC) are still poorly understood. It has been determined that microRNA (miRNA) expression has tissue and cell specific, and decreased expression of specific miRNA could induce tumor genesis or metastasis. In this study, we identified that miR-17-5p was expressed lower in high metastatic capability HCC cell lines HCCLM3 and MHCC97H than low metastatic HCC cell line HepG2 by real-time (RT)-PCR. Restoration of miR-17-5p could significantly repress the invasiveness and metastasis of MHCC97H cell line. Furthermore, we validated c-Myc as a downstream and functional target of miR-17-5p using luciferase reporter assay. Immunohistochemical assay revealed that the expression of c-Myc protein levels was significantly increased in cancerous tissues compared with para-tumor tissues. After clinical data analysis, we observed that the higher level of c-Myc was significantly associated with a reduced overall survival (p = 0.0209). Consistent with previous research, we also demonstrated that c-Myc could upregulate the expression of miR-17-5p. Taken together, our data indicated that there is a regulatory feedback loop between miR-17-5p and c-Myc, in which miR-17-5p could suppress some of the distinguishing features, invasion, and metastasis, of oncogenic c-Myc in HCC cells, and meanwhile, miR-17-5p is upregulated by c-Myc role as a transcription factor, although further studies are still needed.

Keywords

Hepatocellular carcinoma (HCC) miR-17-5p c-Myc Regulatory feedback loop Metastasis Invasion 

Notes

Acknowledgments

The project was jointly supported by the National Science Foundation of China (81272437, 81472675).

Compliance with ethical standards

All procedures were approved by the Zhongshan Hospital Research Ethics Committee. Informed consent was obtained from each patient according to regulations set forth by the Ethics Committee.

Conflicts of interest

None

Authors’ contributions

DL Liu, LL Dong, and WZ Wu conceived and designed the study. DL Liu, LL Dong, Y Liu, and D Wen performed the experiments including IHC, RT-PCR, Western blotting and in vivo assays. DL Liu and LL Dong performed luciferase reporter assays. DL Liu, LL Dong, and WZ Wu analyzed the data and prepared the manuscript. DM Gao, HC Sun, and J Fan participated in the study design. All authors read and approved the final manuscript.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Dongli Liu
    • 1
  • Lili Dong
    • 1
  • Yang Liu
    • 1
  • Duo Wen
    • 2
  • Dongmei Gao
    • 1
  • Huichuan Sun
    • 1
  • Jia Fan
    • 1
    • 3
  • Weizhong Wu
    • 1
  1. 1.Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of EducationShanghaiChina
  2. 2.Department of Medical Oncology, Shanghai Cancer CenterFudan UniversityShanghaiChina
  3. 3.Institute of Biomedical SciencesFudan UniversityShanghaiChina

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