miR-19a/b and MeCP2 repress reciprocally to regulate multidrug resistance in gastric cancer cells

Zhu,Fei; Wu,Qiong; Ni,Zhen; Lei,Chao; Li,Ting; Shi,Yongquan

doi:10.3892/ijmm.2018.3581

miR-19a/b and MeCP2 repress reciprocally to regulate multidrug resistance in gastric cancer cells

Authors:
- Fei Zhu
- Qiong Wu
- Zhen Ni
- Chao Lei
- Ting Li
- Yongquan Shi
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Affiliations: State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: March 22, 2018 https://doi.org/10.3892/ijmm.2018.3581
Pages: 228-236
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Despite the improvement in gastric cancer (GC) treatment, multidrug resistance (MDR) is still a significant reason for chemotherapy failure. Our previous studies have demonstrated that miR-19a/b upregulation directly promoted MDR in GC cells. However, the exact regulation and the potential molecule mechanisms have not been fully clarified. In this study, we found that miR-19a/b was directly involved in 5-aza-2'-deoxycytidine (5-Aza-dC) induced MDR of GC cells. Mechanically, demethylation of miR-19a/b repressed methyl CpG binding protein 2 (MeCP2) expression via direct binding at the 3'-untranslated regions, which then alleviated the inhibitory effects of MeCP2 on miR-19a/b expression. Thus, the mutual regulatory network sustains preservation of the expression levels of miR-19a/b. We further demonstrated that miR-19a/b expression was inversely correlated to MeCP2 expression in GC tissues. These data showed an intimate interplay among miR-19a/b methylation, MeCP2 activity, and MDR, revealing a potential therapeutic target for GC.

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