title: Combinatorial effects of miR-20a and miR-29b on neuronal apoptosis induced by spinal cord injury.
abstract: Neuronal apoptosis is one of the prominent features involved in spinal cord injury (SCI). MicroRNAs (miRNAs) are small non-coding RNAs that functions in a variety of cellular processes including apoptosis. MiRNAs have been implicated as effectors of SCI. However, role of miRNAs in SCI-associated neuronal apoptosis remains to be investigated. A number of bioinformatics approaches have suggested Mcl-1 and BH3-only family genes as potential downstream targets regulated by miR-20a and miR-29b, respectively. To determine whether miR-20a and miR-29b play a role in neuronal apoptosis of SCI by regulating those genes, we transfected Neuro-2A neuroblastoma cells with mimic and inhibitor for the two miRNAs. The miR-20a mimic decreased Mcl-1 expression and the miR-29b mimic reduced the expression of Bad, Bim, Noxa and Puma. The repressor role of miR-20a and miR-29b is confirmed by the transfection of Neuro-2A cells with their inhibitor. Moreover, miR-20a mimic or miR-29b inhibitor attenuated Neuro-2A cell viability and co-transfection of both further diminished the viability of these cells. The in vitro effects of miR-20a and miR-29b on neuronal apoptosis were corroborated by the in vivo studies. Injection of miR-20a mimic or miR-29b inhibitor into the lesion of the injured spinal cord rescued the neuronal death and co-injection of both completely abolished SCI-induced apoptosis. In conclusion, altered expression of miR-20a and miR-29b may cooperatively contribute to the neuronal cell death of SCI through down-regulating anti-apoptotic myeloid cell leukemia sequence-1 (Mcl-1) and up-regulating pro-apoptotic BH3-only proteins.
authors.affiliation: Department of Radiology, Affiliated Hospital of Qingdao University Qingdao 266003, China.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Liu
authors.affiliation: Department of Neurology, Affiliated Hospital of Qingdao University Qingdao 266003, China.
authors.forename: Xue-Ping
authors.initials: XP
authors.lastname: Zheng
authors.affiliation: Neurologial Intensive Care Unit, Affiliated Hospital of Qingdao University Qingdao 266003, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Institute of Integrative Medicine, Qingdao University Qingdao 266003, China.
authors.forename: Yun-Liang
authors.initials: YL
authors.lastname: Guo
authors.affiliation: Organ Transplantation Center, Affiliated Hospital of Qingdao University Qingdao 266003, China.
authors.forename: Jian-Hong
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival; D015536:Down-Regulation; D005260:Female; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; C532375:Mirn20 microRNA, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein
keywords: MicroRNAs; Neuronal apoptosis; myeloid cell leukemia sequence-1; spinal cord injury