miR-145 sensitizes breast cancer to doxorubicin by targeting multidrug resistance-associated protein-1
Gao, Man3; Miao, Lingling3; Liu, Mingxia3; Li, Chenggang3; Yu, Cunzhi3; Yan, Hong3; Yin, Yongxiang2; Wang, Yizheng1; Qi, Xinming3; Ren, Jin3
刊名ONCOTARGET
2016-09-13
卷号7期号:37页码:59714-59726
关键词breast cancer MRP1 miRNA chemoresistance doxorubicin
ISSN号1949-2553
DOI10.18632/oncotarget.10845
文献子类Article
英文摘要Multidrug resistance-associated protein 1 (MRP1) is an important efflux transporter and overexpression of MRP1 usually leads to chemoresistance in breast cancer. Here, we found MRP1 overexpressed in human breast cancer tissues and breast cancer cell lines (compared with normal breast tissues and cell line, respectively). And MRP1 level increased in doxorubicin resistant MCF-7 cells compared with parental MCF-7 cells. Increasing evidences suggest microRNAs (miRNAs) influence chemotherapy response. We found miR-145 level decreased in human breast cancer tissues, breast cancer cell lines and doxorubicin resistant MCF-7 cells, and inversely correlated with MRP1 expression level. In the process of constructing MCF-7 doxorubicin resistant cell line, escalating doxorubicin markedly decreased miR-145 level, following by increased MRP1 level. Further study showed, miR-145 suppressed MRP1 expression by directly targeting MRP1 3'-untranslated regions. Overexpression of miR-145 sensitized breast cancer cells to doxorubicin in vitro and enhanced to doxorubicin chemotherapy in vivo through inducing intracellular doxorubicin accumulation via inhibiting MRP1. Taken together, our study revealed miR-145 sensitizes breast cancer to doxorubicin by targeting MRP1 and indicated the potential application in developing MRP1 inhibitor.
资助项目National Science and Technology Major Project of China[2015ZX09102005]
WOS关键词REVERSAL AGENTS ; EXPRESSION ; ABCC1 ; CHEMORESISTANCE ; MICRORNAS ; CELLS ; MECHANISM ; THERAPY ; PATHWAY ; FUTURE
WOS研究方向Oncology ; Cell Biology
语种英语
出版者IMPACT JOURNALS LLC
WOS记录号WOS:000387153900075
内容类型期刊论文
源URL[http://119.78.100.183/handle/2S10ELR8/275892]  
专题药物安全性评价中心
通讯作者Qi, Xinming; Ren, Jin
作者单位1.Beijing Inst Basic Med Sci, Brain Sci Ctr, Beijing, Peoples R China
2.Nanjing Med Univ, Wuxi Matern & Children Hlth Hosp, Dept Pathol, Wuxi, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Shanghai, Peoples R China;
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GB/T 7714
Gao, Man,Miao, Lingling,Liu, Mingxia,et al. miR-145 sensitizes breast cancer to doxorubicin by targeting multidrug resistance-associated protein-1[J]. ONCOTARGET,2016,7(37):59714-59726.
APA Gao, Man.,Miao, Lingling.,Liu, Mingxia.,Li, Chenggang.,Yu, Cunzhi.,...&Ren, Jin.(2016).miR-145 sensitizes breast cancer to doxorubicin by targeting multidrug resistance-associated protein-1.ONCOTARGET,7(37),59714-59726.
MLA Gao, Man,et al."miR-145 sensitizes breast cancer to doxorubicin by targeting multidrug resistance-associated protein-1".ONCOTARGET 7.37(2016):59714-59726.
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