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

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.

SUBMITTER: Zhu F 

PROVIDER: S-EPMC5979884 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature