title: An integrated analysis of differential miRNA and mRNA expressions in human gallstones.
abstract: Gallstone disease, including cholesterol precipitation in bile, increased bile salt hydrophobicity and gallbladder inflammation. Here, we investigated miRNA and mRNA involved in the formation of gallstones, and explored the molecular mechanisms in the development of gallstones. Differentially expressed 17 miRNAs and 525 mRNA were identified based on Illumina sequencing from gallbladder mucosa of patients with or without gallstones, and were validated by randomly selected 6 miRNAs and 8 genes using quantitative RT-PCR. 114 miRNA target genes were identified, whose functions and regulating pathways were related to gallstones. The differentially expressed genes were enriched upon lipoprotein binding and some metabolic pathways, and differentially expressed miRNAs enriched upon ABC transportation and cancer related pathways. A molecular regulatory network consisting of 17 differentially expressed miRNAs, inclusive of their target genes, was constructed. miR-210 and its potential target gene ATP11A were found to be differentially expressed in both miRNA and mRNA profiles. ATP11A was a direct target of miR-210, which was predicted to regulate the ABC-transporters pathway. The expression levels of ATP11A in the gallstone showed inverse correlation with miR-210 expression, and up-regulation of miR-210 could reduce ATP11A expression in HGBEC. This is the first report that indicates the existence of differences in miRNA and mRNA expression in patients with or without gallstones. Our data shed light on further investigating the mechanisms of gallstone formation.
authors: Department of Hepatobiliary Surgery, the 1st Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors: Bin
authors: B
authors: Yang
authors: Bin
authors: B
authors: Liu
authors: Pinduan
authors: P
authors: Bi
authors: Tao
authors: T
authors: Wu
authors: Qiang
authors: Q
authors: Wang
authors: Jie
authors: J
authors: Zhang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D030562:Databases, Protein; D005704:Gallbladder / Q000166:cytology; D042882:Gallstones / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D018528:ATP-Binding Cassette Transporters; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C548142:ATP11A protein, human