title: MicroRNA-23a/b and microRNA-27a/b suppress Apaf-1 protein and alleviate hypoxia-induced neuronal apoptosis.
abstract: Expression of apoptotic protease activating factor-1 (Apaf-1) gradually decreases during brain development, and this decrease is likely responsible for the decreased sensitivity of brain tissue to apoptosis. However, the mechanism by which Apaf-1 expression is decreased remains elusive. In the present study, we found that four microRNAs (miR-23a/b and miR-27a/b) of miR-23a-27a-24 and miR-23b-27b-24 clusters play key roles in modulating the expression of Apaf-1. First, we found that miR-23a/b and miR-27a/b suppressed the expression of Apaf-1 in vitro. Interestingly, the expression of the miR-23-27-24 clusters in the mouse cortex gradually increased in a manner that was inversely correlated with the pattern of Apaf-1 expression. Second, hypoxic injuries during fetal distress caused reduced expression of the miR-23b and miR-27b that was inversely correlated with an elevation of Apaf-1 expression during neuronal apoptosis. Third, we made neuronal-specific transgenic mice and found that overexpressing the miR-23b and miR-27b in mouse neurons inhibited the neuronal apoptosis induced by intrauterine hypoxia. In conclusion, our results demonstrate, in central neural system, that miR-23a/b and miR-27a/b are endogenous inhibitory factors of Apaf-1 expression and regulate the sensitivity of neurons to apoptosis. Our findings may also have implications for the potential target role of microRNAs in the treatment of neuronal apoptosis-related diseases.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Q
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, Jiangsu, China.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: S
authors.initials: S
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: F
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, Jiangsu, China.
authors.forename: K
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, Jiangsu, China.
authors.forename: C-Y
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, Jiangsu, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005311:Fetal Hypoxia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; C540674:Mirn27 microRNA, mouse