title: miR-27b synergizes with anticancer drugs via p53 activation and CYP1B1 suppression.
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.
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, Shanghai 200031, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Mu
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, Shanghai 200031, China.
authors.forename: Chaobo
authors.initials: C
authors.lastname: Hu
authors.affiliation: Eastern Hepatobilliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Haibin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Eastern Hepatobilliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Qu
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, Shanghai 200031, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Cen
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, Shanghai 200031, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210000, China.
authors.forename: Haozhen
authors.initials: H
authors.lastname: Ren
authors.affiliation: Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Xianghuo
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210000, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, Shanghai 200031, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Hui
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics; D000077157:Sorafenib; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D010671:Phenylurea Compounds; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D009536:Niacinamide; D000077157:Sorafenib; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1