title: The transcription factor c-Myc suppresses MiR-23b and MiR-27b transcription during fetal distress and increases the sensitivity of neurons to hypoxia-induced apoptosis.
abstract: Previous studies reported that the expression of miR-23b-27b cluster was downregulated in embryonic brain cortices during hypoxia-induced neuronal apoptosis. However, the mechanism underlying this downregulation is not completely understood. Here, we report that the transcription factor c-Myc plays an important role in regulating the expression of miR-23b-27b cluster during hypoxia. First, the c-Myc protein level was significantly elevated in embryonic brain cortices in a mouse model of fetal distress. Second, forced overexpression or knockdown of c-Myc could suppress or increase the expression of miR-23b-27b cluster polynucleotides. Third, we identified 2 conserved c-Myc binding sites (E-boxes) in the enhancer and promoter regions of miR-23b-27b cluster in the mouse genome. Finally, we showed that elevated c-Myc expression led to an increase in the Apaf-1 level by suppressing miR-23b-27b cluster expression and that this enhanced neuronal sensitivity to apoptosis. In summary, our study demonstrates that c-Myc may suppress the expression of the miR-23b-27b cluster, resulting in additional neuronal apoptosis during hypoxia.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Zhengya
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Laboratory of Neurodegenerative Diseases and Repair, Yancheng Institute of Health Sciences, Yancheng, China.
authors.forename: Anyang
authors.initials: A
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Chen-yu
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Qipeng
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis*; D009474:Neurons / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D020218:Response Elements; D014158:Transcription, Genetic
chemical_list: D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; C540674:Mirn27 microRNA, mouse; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc