title: PKHD1 post-transcriptionally modulated by miR-365-1 inhibits cell-cell adhesion.
abstract: Autosomal recessive polycystic kidney disease (ARPKD) is a severe inherited disorder with an incidence of 1/20 000 live births. Mutations of PKHD1 (polycystic kidney and hepatic disease gene 1) gene were identified to be responsible for ARPKD. However, the underlying molecular mechanisms remain largely unknown. MicroRNAs (miRNAs) are an abundant class of small RNAs with global effect on gene expression. Up to 30% of human protein coding genes may be regulated by miRNAs. However, to date, nothing is known regarding the role of miRNAs in PKHD1. In this study, we exploited bioinformatics to analyse the 3'UTR of PKHD1 gene and illustrated that the 3'UTR region of the gene is highly conserved in evolution. We identified about 35 candidate miRNAs within a 3738 bp window of the 3'UTR region. Of the 35 potential miRNAs, miR-365-1 emerged to post-transcriptionally modulate the expression of PKHD1. Furthermore, we demonstrated that miR-365-1 modulated PKHD1 suppressed cell-cell adhesion in part through E-cadherin.
authors.affiliation: Core Facility of Genetically Engineered Mice, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Duan
authors.forename: Huizhe
authors.initials: H
authors.lastname: Huang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lv
authors.forename: Honglian
authors.initials: H
authors.lastname: Wang
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Tang
authors.forename: Huan
authors.initials: H
authors.lastname: Sun
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Li
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Ai
authors.forename: Ruizhi
authors.initials: R
authors.lastname: Tan
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Liu
authors.forename: Mianzhi
authors.initials: M
authors.lastname: Chen
authors.forename: Weiwei
authors.initials: W
authors.lastname: Duan
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002478:Cells, Cultured; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C546819:MIRN365 microRNA, human; D035683:MicroRNAs; C451750:PKHD1 protein, human; D011956:Receptors, Cell Surface