Epigenetically deregulated miR-200c is involved in a negative feedback loop with DNMT3a in gastric cancer cells

  • Authors:
    • Yingfei Li
    • Yuqiang Nie
    • Sanfang Tu
    • Hong Wang
    • Yongjian Zhou
    • Yanlei Du
    • Jie Cao
    • Min Ye
  • View Affiliations

  • Published online on: August 2, 2016     https://doi.org/10.3892/or.2016.4996
  • Pages: 2108-2116
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Abstract

Aberrant methylation of miRNAs is commonly observed in cancers. In the present study, we investigated the regulation of the miR-200 family and its role in regulating DNA methylation events in gastric cancer (GC). We demonstrated that miR‑200c was aberrantly expressed in GC and associated with histologic type and tumor progression. Hypermethylation of the promoter region was found to be responsible for the loss of miR-200c in GC cells. Demethylation agents led to recovery of miR-200c expression in GC cell lines. Moreover, DNMT3a knockdown abolished the hypermethylation of the miR-200c gene and induced upregulation of miR-200c expression, whereas ectopic DNMT3a expression increased miR-200c promoter methylation and decreased miR-200c expression. Conversely, transfection of miR-200c led to downregulation of DNMT3a protein and induced endogenous pre-miR-200c and pri-miR‑200c re-expression. Luciferase assays confirmed miR‑200c binding to the DNMT3a 3'UTR. Finally, ectopic expression of miR-200c or knockdown of DNMT3a expression impeded GC cell growth, migration and invasion. Taken together, these observations demonstrates a novel epigenetic feedback loop between miR-200c and DNMT3a in the carcinogenesis and progression of GC.
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October-2016
Volume 36 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Li Y, Nie Y, Tu S, Wang H, Zhou Y, Du Y, Cao J and Ye M: Epigenetically deregulated miR-200c is involved in a negative feedback loop with DNMT3a in gastric cancer cells. Oncol Rep 36: 2108-2116, 2016
APA
Li, Y., Nie, Y., Tu, S., Wang, H., Zhou, Y., Du, Y. ... Ye, M. (2016). Epigenetically deregulated miR-200c is involved in a negative feedback loop with DNMT3a in gastric cancer cells. Oncology Reports, 36, 2108-2116. https://doi.org/10.3892/or.2016.4996
MLA
Li, Y., Nie, Y., Tu, S., Wang, H., Zhou, Y., Du, Y., Cao, J., Ye, M."Epigenetically deregulated miR-200c is involved in a negative feedback loop with DNMT3a in gastric cancer cells". Oncology Reports 36.4 (2016): 2108-2116.
Chicago
Li, Y., Nie, Y., Tu, S., Wang, H., Zhou, Y., Du, Y., Cao, J., Ye, M."Epigenetically deregulated miR-200c is involved in a negative feedback loop with DNMT3a in gastric cancer cells". Oncology Reports 36, no. 4 (2016): 2108-2116. https://doi.org/10.3892/or.2016.4996