Volume 25, No 4, Apr 2015
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 25 Issue 4, April 2015: 477-495
ORIGINAL ARTICLES
miR-27b synergizes with anticancer drugs via p53 activation and CYP1B1 suppression
Wenjing Mu1,*, Chaobo Hu1,*, Haibin Zhang2,*, Zengqiang Qu2, Jin Cen1, Zhixin Qiu1, Chao Li3, Haozhen Ren4, Yixue Li3, Xianghuo He5, Xiaolei Shi4 and Lijian Hui1
1State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, Shanghai 200031, China
2Eastern Hepatobilliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
3Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
4Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210000, China
5Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
Correspondence: Lijian Hui; Xiaolei Shi(ljhui@sibcb.ac.cn; njsxl2000@163.com)
Liver and kidney cancers are notorious for drug resistance. Due to the complexity, redundancy and interpatient heterogeneity of resistance mechanisms, most efforts targeting a single pathway were unsuccessful. Novel personalized therapies targeting multiple essential drug resistance pathways in parallel hold a promise for future cancer treatment. Exploiting the multitarget characteristic of microRNAs (miRNAs), we developed a new therapeutic strategy by the combinational use of miRNA and anticancer drugs to increase drug response. By a systems approach, we identified that miR-27b, a miRNA deleted in liver and kidney cancers, sensitizes cancer cells to a broad spectrum of anticancer drugs in vitro and in vivo. Functionally, miR-27b enhances drug response by activating p53-dependent apoptosis and reducing CYP1B1-mediated drug detoxification. Notably, miR-27b promotes drug response specifically in patients carrying p53-wild-type or CYP1B1-high signature. Together, we propose that miR-27b synergizes with anticancer drugs in a defined subgroup of liver and kidney cancer patients.
10.1038/cr.2015.23
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