title: MicroRNA-30c-1-3p is a silencer of the pregnane X receptor by targeting the 3'-untranslated region and alters the expression of its target gene cytochrome P450 3A4.
abstract: The pregnane X receptor (PXR) is a master regulator of genes involved in drug elimination. Recently, activation of PXR has also been linked to the development of many disease conditions such as metabolic disorders and malignancies. MicroRNAs (miRs) emerge as important molecular species involved in these conditions. This study was undertaken to test a large number of miRs for their ability to regulate PXR expression. As many as 58 miRs were tested and miR-30c-1-3p was identified to suppress PXR expression. The suppression was achieved by targeting the 3'-untranslated region, 438 nucleotides from the stop codon. The suppression was detected in multiple cell lines from different organ origins. In addition, miR-30c-1-3p altered basal and induced expression of cytochrome P450 3A4 (CYP3A4), a prototypical target gene of PXR. The alteration varied depending on the time and amounts of miR-30c-1-3p. CYP3A4 is responsible for the metabolism of more than 50% medicines. The interconnection between miR-30c-1-3p and PXR signifies a role of miRs in drug-drug interactions and chemosensitivity. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, Center for Integrated Drug Development, University of Rhode Island, Kingston, RI 02881, United States.
authors.forename: Thaveechai
authors.initials: T
authors.lastname: Vachirayonstien
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, Center for Integrated Drug Development, University of Rhode Island, Kingston, RI 02881, United States. Electronic address: byan@uri.edu.
authors.forename: Bingfang
authors.initials: B
authors.lastname: Yan
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D045744:Cell Line, Tumor; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D008156:Luciferases; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
keywords: Chemosensitivity; Drug–drug interaction; MicroRNA CYP3A4; Nuclear receptor; PXR