MicroRNAs Differentially Regulate Carbonyl Reductase 1 (CBR1) Gene Expression Dependent on the Allele Status of the Common Polymorphic Variant rs9024 英文参考文献.docVIP

下载本文档

6
0
约3.49万字
约 9页
2017-05-12 发布于上海
举报
版权申诉

MicroRNAs Differentially Regulate Carbonyl Reductase 1 (CBR1) Gene Expression Dependent on the Allele Status of the Common Polymorphic Variant rs9024 英文参考文献.doc

1、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。。
2、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
3、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
4、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
5、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
6、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
7、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

MicroRNAs Differentially Regulate Carbonyl Reductase 1 (CBR1) Gene Expression Dependent on the Allele Status of the Common Polymorphic Variant rs9024 英文参考文献

MicroRNAsDifferentiallyRegulateCarbonylReductase1 (CBR1)GeneExpressionDependentontheAlleleStatus oftheCommonPolymorphicVariantrs9024 JamesL.Kalabus,QiuyingCheng,JavierG.Blanco* DepartmentofPharmaceuticalSciences,TheStateUniversityofNewYorkatBuffalo,Buffalo,NewYork,UnitedStatesofAmerica Abstract MicroRNAs(miRNAs)aresmallRNAsresponsibleforthepost-transcriptionalregulationofavarietyofhumangenes.Todate, theirinvolvementintheregulationofCBR1isunknown.ThisstudyreportsforthefirsttimetheidentificationofmicroRNA- 574-5p(hsa-miR-574-5p)andmicroRNA-921(hsa-miR-921)astwomiRNAscapableofinteractingwiththe39-untranslated region (39-UTR) of the CBR1 gene and downregulating CBR1 expression. Furthermore, we demonstrate that a common single-nucleotidepolymorphism(SNP)intheCBR139-UTR(rs9024,CBR11096G.A)differentiallyimpactstheregulationof CBR1byhsa-miR-574-5pandhsa-miR-921dependentongenotype.First,fourcandidatemiRNAswereselectedbasedon bioinformatic analyses, and were tested in Chinese hamster ovary (CHO) cells transfected with CBR1 39-UTR constructs harboring either the G or A allele for rs9024. We found that hsa-miR-574-5p and hsa-miR-921 significantly decreased luciferaseactivityinCHOcellstransfectedwiththeCBR139-UTRconstructcarryingthemajorrs9024Galleleby35%and 46%,respectively.TheinfluenceofthesemiRNAswasdifferentincellstransfectedwithaCBR139-UTRconstructcontaining theminorrs9024Aalleleinthatonlyhsa-miR-574-5phadademonstrableeffect(i.e.,52%decreaseinlucifersaseactivity).To further determine the functional effects of miRNA-mediated regulation of polymorphic CBR1, we assessed CBR1 protein expressionandCBR1enzymaticactivityfortheprototypicalsubstratemenadioneinhumanlymphoblastoidcelllineswith distinctrs9024genotypes.Wefoundthathsa-miR-574-5pandhsa-miR-921significantlydecreasedCBR1protein(48%and 40%,respectively)andCBR1menadioneactivity(54%and18%,respectively)inlymphoblastoidcellshomozygousforthe majorrs9024Gallele.Incontrast,onlyhsa-miR-574-5pdecreasedCBR1proteinandCBR1activityince