MicroRNA-19a/b regulates multidrug resistance in human gastric cancer cells by targeting PTEN

被引：191
作者：
Wang, Fang [1 ,2 ,3 ]
Li, Ting [1 ,2 ]
Zhang, Bin [4 ]
Li, Hong [1 ,2 ]
Wu, Qiong [1 ,2 ]
Yang, Li [3 ]
Nie, Yongzhan [1 ,2 ]
Wu, Kaichun [1 ,2 ]
Shi, Yongquan [1 ,2 ]
Fan, Daiming [1 ,2 ]
机构：
[1] Fourth Mil Med Univ, State Key Lab Canc Biol, Xian 710032, Shaanxi, Peoples R China
[2] Fourth Mil Med Univ, Xijing Hosp Digest Dis, Xijing Hosp, Xian 710032, Shaanxi, Peoples R China
[3] Ningxia Med Univ, Affiliated Hosp, Dept Gastroenterol, Yinchuan 750004, Ningxia, Peoples R China
[4] Fourth Mil Med Univ, Sch Aerosp Med, Xian 710032, Shaanxi, Peoples R China
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2013年 / 434卷 / 03期
基金：
中国国家自然科学基金;
关键词：
miR-19a/b; Gastric cancer; Multidrug resistance; PTEN; MDR1; GENE-EXPRESSION; DRUG-RESISTANCE; ADJUVANT CHEMOTHERAPY; APOPTOSIS; CHEMORESISTANCE; MECHANISMS; INDUCTION; RESECTION; PROFILES; PATHWAY;
D O I：
10.1016/j.bbrc.2013.04.010
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：688 / 694
页数：7
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