141139 20240321220929.0 10.2174/2211536607666180821162403 doi pmid:30147021 pmid 2211-5366 ISSN 2211-5374 ISSN DZNE-2020-07461 English 570 Krauß, Sybille P:(DE-2719)2421562 0 First author Upregulation of miR-25 and miR-181 Family Members Correlates with Reduced Expression of ATXN3 in Lymphocytes from SCA3 Patients. Sharjah [u.a.] 2019 Bentham Science print Crossref Bentham Science Publishers Ltd. 2018-11-27 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1700147394_27198 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Spinocerebellar ataxia type 3 (SCA3), the most common spinocerebellar ataxia, is caused by a polyglutamine (polyQ) expansion in the protein ataxin-3 (ATXN3). Silencing the expression of polyQ-expanded ATXN3 rescues the cellular disease phenotype.This study investigated the differential expression of microRNAs (miRNAs), small noncoding RNAs targeting gene expression, in lymphoblastoid cells (LCs) from SCA3 patients and the capability of identified deregulated miRNAs to target and alter ATXN3 expression.MiRNA profiling was performed by microarray hybridization of total RNA from control and SCA3-LCs. The capability of the identified miRNAs and their target sites to suppress ATXN3 expression was analyzed using mutagenesis, reverse transcription PCR, immunoblotting, luciferase reporter assays, mimics and precursors of the identified miRNAs.SCA3-LCs showed significantly decreased expression levels of ATXN3 and a significant upregulation of the ATXN3-3'UTR targeting miRNAs, miR-32 and miR-181c and closely related members of the miR-25 and miR-181 family, respectively. MiR-32 and miR-181c effectively targeted the 3'UTR of ATXN3 and suppressed the expression of ATXN3.The simultaneous upregulation of closely related miRNAs targeting the 3'UTR of ATXN3 and the significantly reduced ATXN3 expression levels in SCA3-LCs suggests that miR-25 and miR-181 family members cooperatively bind to the 3'UTR to suppress the expression of ATXN3. The findings further suggest that the upregulation of miR-25 and miR-181 family members in SCA3- LCs reflects a cell type-specific, protective mechanism to diminish polyQ-mediated cytotoxic effects. Thus, miRNA mimics of miR-25 and miR-181 family members may prove useful for the treatment of SCA3. 342 - Disease Mechanisms and Model Systems (POF3-342) G:(DE-HGF)POF3-342 POF3-342 POF III 0 2018-11-27 Crossref https://creativecommons.org/licenses/by/4.0/legalcode Dataset connected to CrossRef, PubMed, 3' Untranslated Regions NLM Chemicals MIRN25 microRNA, human NLM Chemicals MIrn181 microRNA, human NLM Chemicals MicroRNAs NLM Chemicals Repressor Proteins NLM Chemicals ATXN3 protein, human EC 3.4.19.12 NLM Chemicals Ataxin-3 EC 3.4.19.12 NLM Chemicals 3' Untranslated Regions MeSH Ataxin-3: genetics MeSH Ataxin-3: metabolism MeSH HeLa Cells MeSH Humans MeSH Lymphocytes: metabolism MeSH Machado-Joseph Disease: genetics MeSH Machado-Joseph Disease: metabolism MeSH MicroRNAs: genetics MeSH MicroRNAs: metabolism MeSH Repressor Proteins: genetics MeSH Repressor Proteins: metabolism MeSH Nalavade, Rohit P:(DE-2719)2809904 1 Weber, Stephanie P:(DE-2719)2662310 2 Carter, Katlynn P:(DE-HGF)0 3 Evert, Bernd O P:(DE-HGF)0 4 10.2174/2211536607666180821162403 : Bentham Science Publishers Ltd., 2018-11-27 1 76-85 journal-article Crossref MicroRNA 8 2018 2211-5366 10.2174/2211536607666180821162403 Vol. 8, no. 1, p. 76 - 85 PERI:(DE-600)2800970-8 1 8:1<76 - 85 76-85 MicroRNA 8 2019 2211-5366 http://pub.dzne.de/record/141139/files/DZNE-2020-07461_Restricted.pdf http://pub.dzne.de/record/141139/files/DZNE-2020-07461_Restricted.pdf?subformat=pdfa pdfa VDB oai:pub.dzne.de:141139 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)2421562 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)2809904 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2662310 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-342 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Disease Mechanisms and Model Systems 0 2019 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-19 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-19 I:(DE-2719)1011006 AG Krauß Regulatory RNA-protein interaction in neurodegenerative diseases 0 journal VDB I:(DE-2719)1011006 UNRESTRICTED -- missing cx lookup -- 10.1016/j.pneurobio.2011.11.006 Crossref 10.1016/j.pneurobio.2011.11.006 -- missing cx lookup -- 10.1038/ng1194-221 Crossref 10.1038/ng1194-221 -- missing cx lookup -- 10.1159/000090035 Crossref 10.1159/000090035 -- missing cx lookup -- 10.1001/archneur.58.11.1821 Crossref 10.1001/archneur.58.11.1821 -- missing cx lookup -- 10.1093/hmg/ddg344 Crossref 10.1093/hmg/ddg344 -- missing cx lookup -- 10.1074/jbc.M310939200 Crossref 10.1074/jbc.M310939200 -- missing cx lookup -- 10.1093/hmg/ddr197 Crossref 10.1093/hmg/ddr197 -- missing cx lookup -- 10.1016/j.cell.2009.04.042 Crossref 10.1016/j.cell.2009.04.042 -- missing cx lookup -- 10.1096/fj.06-7002com Crossref 10.1096/fj.06-7002com -- missing cx lookup -- 10.1016/j.bbrc.2007.08.062 Crossref 10.1016/j.bbrc.2007.08.062 -- missing cx lookup -- 10.1523/JNEUROSCI.4540-06.2007 Crossref 10.1523/JNEUROSCI.4540-06.2007 -- missing cx lookup -- 10.1093/hmg/ddp274 Crossref 10.1093/hmg/ddp274 -- missing cx lookup -- 10.1016/j.nbd.2009.07.020 Crossref 10.1016/j.nbd.2009.07.020 -- missing cx lookup -- 10.1371/journal.pone.0005834 Crossref 10.1371/journal.pone.0005834 -- missing cx lookup -- 10.1093/hmg/ddr203 Crossref 10.1093/hmg/ddr203 -- missing cx lookup -- 10.1038/nature10671 Crossref 10.1038/nature10671 -- missing cx lookup -- 10.1093/brain/aws177 Crossref 10.1093/brain/aws177 -- missing cx lookup -- 10.1093/jmcb/mjq005 Crossref 10.1093/jmcb/mjq005 -- missing cx lookup -- 10.1371/journal.pone.0003341 Crossref 10.1371/journal.pone.0003341 -- missing cx lookup -- 10.1093/hmg/ddq111 Crossref 10.1093/hmg/ddq111 -- missing cx lookup -- 10.1038/mt.2013.152 Crossref 10.1038/mt.2013.152 -- missing cx lookup -- 10.3389/fncel.2013.00178 Crossref 10.3389/fncel.2013.00178 -- missing cx lookup -- 10.1016/j.cell.2009.01.002 Crossref 10.1016/j.cell.2009.01.002 -- missing cx lookup -- 10.1016/j.cell.2004.12.035 Crossref 10.1016/j.cell.2004.12.035 -- missing cx lookup -- 10.1016/S0092-8674(03)01018-3 Crossref 10.1016/S0092-8674(03)01018-3 -- missing cx lookup -- 10.1016/j.brainres.2010.03.106 Crossref 10.1016/j.brainres.2010.03.106 -- missing cx lookup -- 10.1016/j.neurobiolaging.2010.03.014 Crossref 10.1016/j.neurobiolaging.2010.03.014 -- missing cx lookup -- 10.1016/j.expneurol.2010.10.012 Crossref 10.1016/j.expneurol.2010.10.012 -- missing cx lookup -- 10.1038/nn.2183 Crossref 10.1038/nn.2183 -- missing cx lookup -- 10.1016/j.febslet.2014.11.013 Crossref 10.1016/j.febslet.2014.11.013 -- missing cx lookup -- 10.1186/2053-8871-1-7 Crossref 10.1186/2053-8871-1-7 -- missing cx lookup -- 10.1016/j.ymthe.2017.01.021 Crossref 10.1016/j.ymthe.2017.01.021 -- missing cx lookup -- 10.1016/j.molcel.2006.07.030 Crossref 10.1016/j.molcel.2006.07.030 -- missing cx lookup -- 10.1371/journal.pone.0059011 Crossref 10.1371/journal.pone.0059011 -- missing cx lookup -- 10.1093/nar/gkm133 Crossref 10.1093/nar/gkm133 -- missing cx lookup -- 10.1016/j.molcel.2016.09.027 Crossref 10.1016/j.molcel.2016.09.027 -- missing cx lookup -- 10.1016/j.febslet.2005.07.070 Crossref 10.1016/j.febslet.2005.07.070 -- missing cx lookup -- 10.1016/j.cell.2007.04.040 Crossref 10.1016/j.cell.2007.04.040 -- missing cx lookup -- 10.1186/s13046-016-0319-x Crossref 10.1186/s13046-016-0319-x -- missing cx lookup -- 10.1038/srep28220 Crossref 10.1038/srep28220 -- missing cx lookup -- 10.3109/00207454.2013.827679 Crossref 10.3109/00207454.2013.827679 -- missing cx lookup -- 10.1186/1476-4598-12-30 Crossref 10.1186/1476-4598-12-30 -- missing cx lookup -- 10.1002/hep.22989 Crossref 10.1002/hep.22989 -- missing cx lookup -- 10.1073/pnas.0806202105 Crossref 10.1073/pnas.0806202105 -- missing cx lookup -- 10.1038/onc.2012.32 Crossref 10.1038/onc.2012.32 -- missing cx lookup -- 10.1128/MCB.00923-08 Crossref 10.1128/MCB.00923-08 -- missing cx lookup -- 10.1158/0008-5472.CAN-08-0144 Crossref 10.1158/0008-5472.CAN-08-0144 -- missing cx lookup -- 10.1073/pnas.1202465109 Crossref 10.1073/pnas.1202465109