MicroRNA-17 post-transcriptionally regulates polycystic kidney disease-2 gene and promotes cell proliferation.
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).
Sun
Huan
H
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.
Li
Qing-Wei
QW
Lv
Xiao-Yan
XY
Ai
Jian-Zhong
JZ
Yang
Qiu-Tan
QT
Duan
Jing-Jing
JJ
Bian
Guo-Hui
GH
Xiao
Yan
Y
Wang
Yi-Dong
YD
Zhang
Zheng
Z
Liu
Yu-Hang
YH
Tan
Rui-Zhi
RZ
Yang
Yang
Y
Wei
Yu-Quan
YQ
Zhou
Qin
Q
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
D020413:3' Untranslated Regions; D035683:MicroRNAs; D050396:TRPP Cation Channels; C524941:MIRN17 microRNA, human