In the current study we investigate the effect of the BA chenodeoxycholic acid (CDCA) on the expression of the miRNAome and mRNAome in primary human hepatocytes (PHHs) and assess to what extent CDCA induces systematic shifts in gene networks responsible for BA and lipid homeostasis as well as drug metabolism. BA-induced shifts in the miRNA profile are set in context to the investigated networks to elucidate novel miRNA driven regulatory pathways influencing the expression of the mentioned gene networks.
Abbreviations in this article: ABC, ATP-binding cassette transporter; AGPAT2, 1-acylglycerol-3-phosphate O-acyltransferase; AhR, arylhydrocarbon receptor; AKR1C1, Aldo-Keto Reductase 1C1; APO, apolipoprotein; ASBT, Apical sodium dependent bile acid transporter; BAs, bile acids; BSEP, bile salt export pump; chenodeoxycholic acid（CDCA）, chenodeoxycholic acid; CPT1A, carnitine palmitoyltransferase 1A; CYP, cytochrome P450; DM, drug metabolism; DMSO, dimethyl sulfoxide; FABP, fatty acid-binding protein; FASN, Fatty acid synthase gene; FDR, false discovery rate; FXR, farnesoid X receptor; HMGCS2, 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2; LDLR, low density lipoprotein receptor; mRNA, messenger RNA; miRNA, microRNA; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NPC1L1, Niemann-Pick C1-Like 1 gene; NTCP, Na+-taurocholate cotransporting polypeptide; OATP, organic anion transport protein; OST, organic solute transporter; PCR, polymerase chain reaction; PHHs, primary human hepatocytes; PPAR-γ, peroxisome proliferator-activated receptor; RT-PCR, real-time PCR; S1PR, Sphingosine-1-phosphate receptor; SHP, small heterodimer partner; SLC, solute carrier family; STARD3, StAR-related lipid transfer domain protein 3; SULT, sulfotransferase; UGT, UDP-glucuronosyltransferase; UTR, untranslated region.
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