miR-27b synergizes with anticancer drugs via p53 activation and CYPIB1 suppression

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 para...

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Bibliographic Details
Published in细胞研究：英文版 no. 4; pp. 477 - 495
Main Author Wenjing Mu Chaobo Hu Haibin Zhang Zengqiang Qu Jin Cen Zhixin Qiu Chao Li Haozhen Ren Yixue Li Xianghuo He Xiaolei Shi Lijian Hui
Format Journal Article
LanguageEnglish
Published 2015
Subjects
miRNA
p53基因
协同作用
微RNA
抗癌药物
激活
癌症患者
癌症治疗
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Summary: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 strat- egy 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 CYP1Bl-mediated drug detoxification. Notably, miR-27b promotes drug response specifically in patients carrying p53-wild-type or CYP1Bl-high signature. Together, we propose that miR-27b synergizes with anticancer drugs in a defined subgroup of liver and kidney cancer patients.
Bibliography:31-1568/Q
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 strat- egy 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 CYP1Bl-mediated drug detoxification. Notably, miR-27b promotes drug response specifically in patients carrying p53-wild-type or CYP1Bl-high signature. Together, we propose that miR-27b synergizes with anticancer drugs in a defined subgroup of liver and kidney cancer patients.
liver cancer; kidney cancer; miR-27b; drug resistance; p53; CYP1B1
ISSN:1001-0602
1748-7838