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Roles of microRNA-330 and Its Target Gene ING4 in the Development of Aggressive Phenotype in Hepatocellular Carcinoma Cells

Digestive Diseases and Sciences volume 62, pages 715–722 (2017)Cite this article

Abstract

Background

Aberrant expression of microRNAs contributes to tumor growth and progression.

Aims

This study was designed to explore the prognostic and biological significance of miR-330 in hepatocellular carcinoma (HCC).

Methods

The expression of miR-330 and its associations with tumor parameters and overall survival were analyzed in HCC patients. The biological functions of miR-330 in HCC cell growth, invasion, and tumorigenesis were investigated. Bioinformatic analysis and luciferase reporter assays were performed to search for potential targets of miR-330.

Results

The miR-330 level was significantly higher in HCCs than in adjacent normal tissues (P = 0.0085). High expression of miR-330 was significantly associated with more aggressive phenotypes and shorter overall survival in HCC. Loss- and gain-of-function studies indicated the favorable effect of miR-330 on tumor cell growth, invasion, and tumorigenesis. Inhibitor of growth 4 (ING4) was identified to be a direct target of miR-330. Overexpression of miR-330 reduced the expression of ING4 in HCC cells. Importantly, restoration of ING4 almost completely reversed the promotion of HCC cell proliferation and invasion by miR-330.

Conclusions

Altogether, this study demonstrates that upregulation of miR-330 is associated with poor prognosis and contributes to more aggressive phenotypes of HCC. The oncogenic role of miR-330 in HCC is linked to downregulation of ING4.

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Acknowledgments

This work was supported by the Youth Foundation of the Affiliated Hospital of Qingdao University of China (Nos. 2192 and 2193).

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Affiliations

  1. Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, China

    Xiao Hu, Yujie Feng, Linlin Qu & Chuandong Sun

  2. Department of ICU, The Affiliated Hospital of Qingdao University, Qingdao, China

    Lin Sun

Authors
  1. Xiao Hu
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  2. Yujie Feng
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  3. Lin Sun
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  4. Linlin Qu
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  5. Chuandong Sun
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Correspondence to Chuandong Sun.

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Hu, X., Feng, Y., Sun, L. et al. Roles of microRNA-330 and Its Target Gene ING4 in the Development of Aggressive Phenotype in Hepatocellular Carcinoma Cells. Dig Dis Sci 62, 715–722 (2017). https://doi.org/10.1007/s10620-016-4429-2

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  • DOI: https://doi.org/10.1007/s10620-016-4429-2

Keywords

  • Growth
  • Invasion
  • microRNA
  • Oncogene
  • Prognosis