MiR-27b Synergizes with Anticancer Drugs Via P53 Activation and CYP1B1 Suppression

Overview

Journal Cell Res

Specialty Cell Biology

Date 2015 Feb 21

PMID 25698578

Citations 47

Authors

Wenjing Mu

Chaobo Hu

Haibin Zhang

Zengqiang Qu

Jin Cen

Zhixin Qiu

Chao Li

Haozhen Ren

Yixue Li

Xianghuo He

Xiaolei Shi

Lijian Hui

Affiliations

Soon will be listed here.

Abstract

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.

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