Journal
DRUG DESIGN DEVELOPMENT AND THERAPY
Volume 11, Issue -, Pages 969-983Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S129305
Keywords
DNA methyltransferase inhibitor; EMT; miRNA; epigenetics; NSCLC
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Funding
- National Natural Science Foundation of China [81372506, 81401897]
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Objective: Epithelial-mesenchymal transition (EMT) is a crucial driver of tumor progression. Tumor growth factor-beta 1 (TGF-beta 1) is an important factor in EMT induction in tumorigenesis. The targeting of EMT may, therefore, represent a promising approach in anticancer treatment. Methods: In this study, we determined the effect of decitabine, a DNA methyltransferase inhibitor, on TGF-beta 1-induced EMT in non-small-cell lung cancer (NSCLC) PC9 and A549 cells. We also assessed the involvement of the miR-200/ZEB axis. Results: Decitabine reversed TGF-beta 1-induced EMT in PC9 cells, but not in A549 cells. This phenomenon was associated with epigenetic changes in the miR-200 family, which regulated EMT by altering the expression of ZEB1 and ZEB2. TGF-beta 1 induced aberrant methylation in miR-200 promoters, leading to EMT in PC9 cells. Decitabine attenuated this effect and inhibited tumor cell migration in vitro and in vivo. In A549 cells, however, neither TGF-beta 1 nor decitabine exhibited an effect on miR-200 promoter methylation. Conclusion: Our findings suggest that epigenetic regulation of the miR-200/ZEB axis is responsible for EMT induction by TGF-beta 1 in PC9 cells. Decitabine inhibits EMT in NSCLC cell PC9 through its epigenetic-based therapeutic activity.
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