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miR-27b Sensitizes Liver Cancer and Kidney Cancer Cells to Multiple Anticancer Drugs

Mar 03, 2015     Email"> PrintText Size

Multidrug resistance is a major obstacle in treating advanced liver cancers and kidney cancers, both refractory to chemotherapeutic drugs and molecular-targeted drugs. Due to impaired liver and kidney functions in patients, it is impractical to enhance therapeutic effect by increasing drug doses. Novel strategies to enhance the sensitivity of current anticancer drugs are urgently needed.

Because cancers are not “addicted” to a single pathway to develop resistance, an emerging trend is toward promoting the sensitivity by targeting multiple resistance pathways in parallel. Exploiting the multi-target characteristic of miRNAs, MU Wenjing, HU Chaobo and their colleagues, led by Prof. HUI Lijian at Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences constitute a novel strategy by the combinational use of miR-27b and anticancer drugs to potentiate therapeutic responses.

miR-27b was identified by an unbiased screening and bioinformatic analyses. It sensitizes cancer cells to a broad spectrum of anticancer drugs in vitro. The combinational use of miR-27b and low dose of anticancer drugs show synergistic therapeutic effect and undetectable side effects in vivo. Mechanistically, miR-27b enhances drug sensitivity through a double-layer regulation, i.e., activating p53-dependent apoptosis and reducing CYP1B1-mediated drug detoxification.

Based on these molecular findings, the researchers found that miR-27b promotes good drug response specifically in patients carrying p53-wild-type or CYP1B1-high gene signature, which suggests a personalized application of miR-27b and anticancer drugs to improve therapeutic effects. 

This work entitled “miR-27b synergizes with anticancer drugs via p53 activation and CYP1B1 suppression” has been published on Cell Research.  

This study is funded by the National Natural Science Foundation of China, the Ministry of Science and Technology of China, and the Science and Technology Commission of Shanghai Municipality. 

 

Figure: miR-27b synergizes with anticancer drugs via at least two essential mechanisms.(Image by Prof. HUI Lijian's group)

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(Editor: CHEN Na)

Contact

HUI Lijian

Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences

Phone:
E-mail: ljhui@sibcb.ac.cn

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