A double-negative feedback loop between EZH2 and miR-26a regulates tumor cell growth in hepatocellular carcinoma

  • Authors:
    • Chunbo Zhuang
    • Pei Wang
    • Da Huang
    • Luming Xu
    • Xiaobei Wang
    • Lin Wang
    • Lihua Hu
  • View Affiliations

  • Published online on: January 13, 2016     https://doi.org/10.3892/ijo.2016.3336
  • Pages: 1195-1204
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Abstract

Accumulating evidence demonstrates the important roles of microRNAs (miRNAs) in tumor development and progression. miR-26a has been reported to be downregulated in several types of cancers including hepatocellular carcinoma, but the underlying mechanism of how miR-26a is repressed remains largely unknown. In the present study, we performed western blot analysis, qRT-PCR, luciferase reporter assay and chromatin immunoprecipitation assay to investigate the relationship between miR-26a and the enhancer of zest homologue 2 (EZH2). CCK-8 assay and colony formation assay were carried out to explore the effect of miR-26a on HCC cells proliferation. We demonstrated that miR-26a was epigenetically repressed by EZH2-mediated H3K27 trimethylation within the miR-26a promoter. Moreover, we confirmed that EZH2 was also a direct target of miR-26a in HCC cells, thus, creating a double-negative feedback loop. Furthermore, miR-26a restoration increased the expressions of its host genes (CTDSPL and CTDSP2). Overexpression of EZH2 abrogated miR-26a induction of CTDSPL and CTDSP2. Restoring the balance of the double-negative feedback loop by miR-26a overpression or EZH2 silence significantly inhibited HCC cell growth. Overexpression of EZH2 rescued the growth inhibition effect of miR-26a. These findings suggest that an imbalanced double-negative feedback loop between EZH2 and miR-26a exists in HCC cells, which contributes to miR-26a deregulation and regulates tumor cells proliferation.
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March 2016
Volume 48 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
APA
Zhuang, C., Wang, P., Huang, D., Xu, L., Wang, X., Wang, L., & Hu, L. (2016). A double-negative feedback loop between EZH2 and miR-26a regulates tumor cell growth in hepatocellular carcinoma. International Journal of Oncology, 48, 1195-1204. https://doi.org/10.3892/ijo.2016.3336
MLA
Zhuang, C., Wang, P., Huang, D., Xu, L., Wang, X., Wang, L., Hu, L."A double-negative feedback loop between EZH2 and miR-26a regulates tumor cell growth in hepatocellular carcinoma". International Journal of Oncology 48.3 (2016): 1195-1204.
Chicago
Zhuang, C., Wang, P., Huang, D., Xu, L., Wang, X., Wang, L., Hu, L."A double-negative feedback loop between EZH2 and miR-26a regulates tumor cell growth in hepatocellular carcinoma". International Journal of Oncology 48, no. 3 (2016): 1195-1204. https://doi.org/10.3892/ijo.2016.3336