title: MicroRNA-17 post-transcriptionally regulates polycystic kidney disease-2 gene and promotes cell proliferation.
abstract: To identify the possible microRNAs (miRNAs) which target the polycystic kidney disease-2 gene (PKD2), and clarify effects of the miRNAs on PKD2. We preliminarily used bioinformatics to analyze 3'UTR (3'untranslated regions) of PKD1 and PKD2 in order to predict the potential microRNAs targeted on them. Subsequently, the stable cell lines with overexpression of microRNA-17 (miR-17) were screened, and luciferase assay combined with the mutation 3'UTR of PKD2 were performed to verify PKD2 is the target of miR-17. Moreover, RT-PCR and Western Blotting were used to determine the post-transcriptionally regulation of PKD2 by miR-17. Finally, MTT cell assays allied with PKD2 rescued strategy were employed to evaluate cell proliferation effects. Our study firstly found that the 3'UTR of PKD2 was more conservation than that of PKD1, and microRNA-17 directly targets the 3'UTR of PKD2 and post-transcriptionally repress the expression of PKD2. Moreover, our findings also demonstrated that overexpression of miR-17 may promote cell proliferation via post-transcriptionally repression of PKD2 in HEK 293T. This suggested that microRNA might be a novel mechanism for cystogenesis as well as a potential therapeutic target for the cell proliferation of autosomal dominant polycystic kidney disease (ADPKD).
authors.affiliation: Core Facility of Genetically Engineered Mice, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 1# Keyuan the Fourth Road, The District of Hi&Tech, Chengdu, Sichuan 610041, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Sun
authors.forename: Qing-Wei
authors.initials: QW
authors.lastname: Li
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Lv
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Ai
authors.forename: Qiu-Tan
authors.initials: QT
authors.lastname: Yang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Duan
authors.forename: Guo-Hui
authors.initials: GH
authors.lastname: Bian
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Yi-Dong
authors.initials: YD
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yu-Hang
authors.initials: YH
authors.lastname: Liu
authors.forename: Rui-Zhi
authors.initials: RZ
authors.lastname: Tan
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D049109:Cell Proliferation; D019295:Computational Biology; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D050396:TRPP Cation Channels / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D050396:TRPP Cation Channels; C524941:MIRN17 microRNA, human