Hypermethylation of miRNA-589 promoter leads to upregulation of HDAC5 which promotes malignancy in non-small cell lung cancer

  • Authors:
    • Changhong Liu
    • Desheng Lv
    • Mo Li
    • Xuefei Zhang
    • Ge Sun
    • Yu Bai
    • Dongmin Chang
  • View Affiliations

  • Published online on: April 20, 2017     https://doi.org/10.3892/ijo.2017.3967
  • Pages:2079-2090
0

Abstract

Histone deacetylases (HDACs) are crucial for regulating chromatin activity, which plays a critical role in cell proliferation, differentiation, and apoptosis of various cancers. Therefore, HDAC inhibitors have been applied as effective therapeutic agents for cancer treatment. However, the expression profiles and regulatory mechanisms of histone deacetylases in lung cancer are not well understood. In the present study, aberrant high levels of HDAC5 were observed in non-small cell lung cancer (NSCLC) and further analysis indicated a negative relationship between HDAC5 and a tumor suppressor, miR‑589‑5p, in NSCLC specimens. Consistently, miR‑589‑5p reduced the expression of HDAC5 by targeting the 3'UTR of HDAC5 mRNA in NSCLC cells. Considering the loss of miR‑589‑5p in NSCLC, the methylation status of the miR-589 gene promoter was examined. The hypermethylation of the miR-589 gene promoter was more significant in NSCLC cells compared with lung epithelial cells, and methylation inhibition by 5-aza-2-deoxycytidine (5-Aza-dC) decreased HDAC5 expression. Furthermore, several downstream gene clusters of HDAC5 were studied in the present investigation. As a result, miR‑589‑5p/HDAC5 pathway was found to regulate a number of cell cycle and epithelial-mesenchymal transition (EMT)-related genes in NSCLC cells. In vitro and in vivo phenotype experiments revealed a critical role of miR‑589‑5p/HDAC5 pathway in the migration, invasion, and tumorigenicity of NSCLC cells. These findings demonstrate a novel mechanism for deregulation of HDAC5 in NSCLC and suggest that miR‑589‑5p/HDAC5 pathway may represent a new prognostic biomarker and therapeutic target against NSCLC.

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June 2017
Volume 50 Issue 6

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

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
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APA
Liu, C., Lv, D., Li, M., Zhang, X., Sun, G., Bai, ., & Chang, D. (2017). Hypermethylation of miRNA-589 promoter leads to upregulation of HDAC5 which promotes malignancy in non-small cell lung cancer. International Journal of Oncology, 50, 2079-2090. https://doi.org/10.3892/ijo.2017.3967
MLA
Liu, C., Lv, D., Li, M., Zhang, X., Sun, G., Bai, ., Chang, D."Hypermethylation of miRNA-589 promoter leads to upregulation of HDAC5 which promotes malignancy in non-small cell lung cancer". International Journal of Oncology 50.6 (2017): 2079-2090.
Chicago
Liu, C., Lv, D., Li, M., Zhang, X., Sun, G., Bai, ., Chang, D."Hypermethylation of miRNA-589 promoter leads to upregulation of HDAC5 which promotes malignancy in non-small cell lung cancer". International Journal of Oncology 50, no. 6 (2017): 2079-2090. https://doi.org/10.3892/ijo.2017.3967