Journal
CELL RESEARCH
Volume 25, Issue 4, Pages 477-495Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cr.2015.23
Keywords
liver cancer; kidney cancer; miR-27b; drug resistance; p53; CYP1B1
Categories
Funding
- National Natural Science Foundation of China [31225016, 81170418, 81125016]
- Ministry of Science and Technology of China [2014CB910601, 2011ZX09307-302-01, 2011CB966304, 2011CB910204]
- Science and Technology Commission of Shanghai Municipality [12JC1409500, 14XD1404200]
- Natural Science Foundation of Jiangsu Province [BK20131084]
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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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