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Article

MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in hepatocellular carcinogenesis

  • Authors:
    • Xiao-Ran Long
    • Yong He
    • Cheng Huang
    • Jun Li
  • View Affiliations / Copyright

    Affiliations: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, P.R. China
  • Pages: 1915-1922
    |
    Published online on: April 8, 2014
       https://doi.org/10.3892/ijo.2014.2373
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Abstract

In general, microRNAs, a class of small (~21 nucleotide) non-coding RNAs, negatively regulate the expression of their target genes. Dysregulation of miRNAs is a common feature in human cancers, but this phenomenon has not been studied extensively in hepatocellular carcinoma (HCC). miR‑148a, a member of the miR-148/152 family, has been found to be downregulated in several tumor types and has been suggested to be a tumor suppressor gene; however, its function in HCC remains unclear. Herein, we describe the epigenetic regulation of miR-148a and its impact on HCC cells. We found that, due to the hypermethylation of its CpG island, miR-148a undergoes methylation-mediated silencing in HCC cell lines. Additionally, DNMT1, the DNA methyltransferase that maintains methylation patterns, is aberrantly upregulated in HCC cell lines, and its overexpression is responsible for hypermethylation of the miR-148a promoter. Intriguingly, the expression of DNMT1, which is a target of miR-148a, is inversely correlated with the expression of miR-148a in HCC cells. These results lead us to propose the existence of a negative feedback regulatory loop between miR-148a and DNMT1 in HCC. Importantly, we demonstrate that the overexpression of miR-148a significantly inhibits HCC cell proliferation and cell cycle progression. Our results suggest the existence of a novel miR-148a-DNMT1 regulatory circuit and indicate that miR-148a acts as a tumor suppressor during hepatocellular carcinogenesis. These results may provide a promising alterative strategy for the therapeutic treatment of HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Long X, He Y, Huang C and Li J: MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in hepatocellular carcinogenesis. Int J Oncol 44: 1915-1922, 2014.
APA
Long, X., He, Y., Huang, C., & Li, J. (2014). MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in hepatocellular carcinogenesis. International Journal of Oncology, 44, 1915-1922. https://doi.org/10.3892/ijo.2014.2373
MLA
Long, X., He, Y., Huang, C., Li, J."MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in hepatocellular carcinogenesis". International Journal of Oncology 44.6 (2014): 1915-1922.
Chicago
Long, X., He, Y., Huang, C., Li, J."MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in hepatocellular carcinogenesis". International Journal of Oncology 44, no. 6 (2014): 1915-1922. https://doi.org/10.3892/ijo.2014.2373
Copy and paste a formatted citation
x
Spandidos Publications style
Long X, He Y, Huang C and Li J: MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in hepatocellular carcinogenesis. Int J Oncol 44: 1915-1922, 2014.
APA
Long, X., He, Y., Huang, C., & Li, J. (2014). MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in hepatocellular carcinogenesis. International Journal of Oncology, 44, 1915-1922. https://doi.org/10.3892/ijo.2014.2373
MLA
Long, X., He, Y., Huang, C., Li, J."MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in hepatocellular carcinogenesis". International Journal of Oncology 44.6 (2014): 1915-1922.
Chicago
Long, X., He, Y., Huang, C., Li, J."MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in hepatocellular carcinogenesis". International Journal of Oncology 44, no. 6 (2014): 1915-1922. https://doi.org/10.3892/ijo.2014.2373
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