title: miR-25 alleviates polyQ-mediated cytotoxicity by silencing ATXN3.
abstract: MicroRNAs (miRNAs) have been reported to play significant roles in the pathogenesis of various polyQ diseases. This study aims to investigate the regulation of ATXN3 gene expression by miRNA. We found that miR-25 reduced both wild-type and polyQ-expanded mutant ataxin-3 protein levels by interacting with the 3'UTR of ATXN3 mRNA. miR-25 also increased cell viability, decreased early apoptosis, and downregulated the accumulation of mutant ataxin-3 protein aggregates in SCA3/MJD cells. These novel results shed light on the potential role of miR-25 in the pathogenesis of SCA3/MJD, and provide a possible therapeutic intervention for this disorder.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Department of Neurology & Institute of Translational Medicine at University of South China, The First People's Hospital of Chenzhou, Chenzhou, PR China.
authors.forename: Fengzhen
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Long
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Chunrong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Huirong
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Junling
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Jiada
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Ranhui
authors.initials: R
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: De-Maw
authors.initials: DM
authors.lastname: Chuang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan 410078, PR China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan 410078, PR China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan 410008, PR China. Electronic address: jianghong73868@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000067699:Ataxin-3; D001483:Base Sequence; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003603:Cytotoxins / Q000633:toxicity*; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics*; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics*; D010455:Peptides / Q000633:toxicity*; D012097:Repressor Proteins / Q000172:deficiency* / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D003603:Cytotoxins; C543351:MIRN25 microRNA, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D012097:Repressor Proteins; C097188:polyglutamine; C092341:ATXN3 protein, human; D000067699:Ataxin-3
keywords: ATXN3; Cytotoxicity; Gene expression regulation; Neuronal intranuclear inclusion; Spinocerebellar ataxia type 3/Machado–Joseph disease; miR-25