MicroRNA-19a/b regulates multidrug resistance in human gastric cancer cells by targeting PTEN
MicroRNA-19a/b regulates multidrug resistance in human gastric cancer cells by targeting PTEN
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DOI：
10.1016/j.bbrc.2013.04.010
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发表时间：
2013-05-10
影响因子：
3.1
通讯作者：
Fan, Daiming
中科院分区：
文献类型：
--
作者：
Wang, Fang;Li, Ting;Fan, Daiming
多药耐药（MDR）是胃癌化疗失败的主要原因。miR-17-92簇的成员，包括miR-19 a/B，被认为是oncomiR，并影响胃癌恶性表型的多个方面。然而，miR-19 a/B在胃癌多药耐药中的作用及其机制尚不清楚。在本研究中，我们发现miR-19 a/B在MDR细胞系中上调。我们的研究结果还表明，miR-19 a/B上调降低了胃癌细胞对抗癌药物的敏感性。我们进一步证实了miR-19 a/B通过增加mdr 1和P-gp的水平来加速胃癌细胞的ADR外排，miR-19 a/B通过调节Bcl-2和Bax来抑制药物诱导的细胞凋亡。最后，我们验证了ART磷酸化抑制剂PTEN是miR-19 a/B的功能靶点。总之，这些发现表明miR-19 a/B通过靶向PTEN促进胃癌细胞的MDR。(C)2013 Elsevier Inc. All rights reserved.
Multidrug resistance (MDR) is the major cause of failure of gastric cancer chemotherapy. Members of the miR-17-92 cluster, including miR-19a/b, are considered oncomiRs and influence multiple aspects of the malignant phenotype of gastric cancer. However, the role of miR-19a/b in MDR in gastric cancer and its underlying mechanism remain unclear. In this study, we found that miR-19a/b were upregulated in MDR cell lines. Our results also showed that miR-19a/b upregulation decreased the sensitivity of gastric cancer cells to anticancer drugs. We further confirmed that miR-19a/b accelerated the ADR efflux of gastric cancer cells by increasing the levels of mdr1 and P-gp and that miR-19a/b suppressed drug-induced apoptosis by regulating Bcl-2 and Bax. Finally, we verified that PTEN, an inhibitor of ART phosphorylation, is the functional target of miR-19a/b. Overall, these findings demonstrated that miR-19a/b promote MDR in gastric cancer cells by targeting PTEN. (C) 2013 Elsevier Inc. All rights reserved.