miR-19a/b and MeCP2 repress reciprocally to regulate multidrug resistance in gastric cancer cells.
miR-19a/b and MeCP2 repress reciprocally to regulate multidrug resistance in gastric cancer cells.
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miR-19a/b和MeCP2相互抑制调节胃癌细胞的多药耐药性
DOI：
10.3892/ijmm.2018.3581
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发表时间：
2018-07
影响因子：
5.4
通讯作者：
Shi Y
中科院分区：
文献类型：
--
作者：
Zhu F;Wu Q;Ni Z;Lei C;Li T;Shi Y
尽管胃癌的治疗水平不断提高，但多药耐药（MDR）仍是导致化疗失败的重要原因。我们前期的研究表明miR-19 a/B的上调直接促进了胃癌细胞的MDR。然而，其确切的调控和潜在的分子机制尚未完全阐明。本研究发现miR-19 a/B直接参与了5-Aza-dC诱导胃癌细胞MDR的过程。在机制上，miR-19 a/B的去甲基化通过直接结合在3′-非翻译区抑制甲基CpG结合蛋白2（MeCP 2）的表达，从而减轻MeCP 2对miR-19 a/B表达的抑制作用。因此，相互调节网络维持miR-19 a/B表达水平的保持。我们进一步证实了胃癌组织中miR-19 a/B的表达与MeCP 2的表达呈负相关。这些数据显示了miR-19 a/B甲基化、MeCP 2活性和MDR之间的密切相互作用，揭示了GC的潜在治疗靶点。
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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DOI：
10.1111/j.1440-1746.2008.05666.x
发表时间：
2009-04-01
影响因子：
4.1
作者：
Guo, Junming;Miao, Ying;Wang, Yanjun
通讯作者：
Wang, Yanjun
影响因子：
9.7
作者：
Fang, JY;Lu, R;Chen, YX
通讯作者：
Chen, YX
影响因子：
6.4
作者：
Wada, Rie;Akiyama, Yoshimitsu;Yuasa, Yasuhito
通讯作者：
Yuasa, Yasuhito
影响因子：
14.9
作者：
Tili E;Michaille JJ;Liu CG;Alder H;Taccioli C;Volinia S;Calin GA;Croce CM
通讯作者：
Croce CM
影响因子：
3.7
作者：
Hashimoto Y;Akiyama Y;Yuasa Y
通讯作者：
Yuasa Y