Transcriptional and post-transcriptional regulation of the pregnane X receptor: a rationale for interindividual variability in drug metabolism.
CYP3A4
Gene expression
Non-coding RNA
Post-transcriptional regulation
Pregnane X receptor
microRNA
Journal
Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
01
07
2020
accepted:
17
09
2020
pubmed:
10
11
2020
medline:
21
10
2021
entrez:
9
11
2020
Statut:
ppublish
Résumé
The pregnane X receptor (PXR, encoded by the NR1I2 gene) is a ligand-regulated transcription factor originally described as a master regulator of xenobiotic detoxification. Later, however, PXR was also shown to interact with endogenous metabolism and to be further associated with various pathological states. This review focuses predominantly on such aspects, currently less covered in literature, as the control of PXR expression per se in the context of inter-individual differences in drug metabolism. There is growing evidence that non-coding RNAs post-transcriptionally regulate PXR. Effects on PXR have especially been reported for microRNAs (miRNAs), which include miR-148a, miR-18a-5p, miR-140-3p, miR-30c-1-3p and miR-877-5p. Likewise, miRNAs control the expression of both transcription factors involved in PXR expression and regulators of PXR function. The impact of NR1I2 genetic polymorphisms on miRNA-mediated PXR regulation is also discussed. As revealed recently, long non-coding RNAs (lncRNAs) appear to interfere with PXR expression. Reciprocally, PXR activation regulates non-coding RNA expression, thus comprising another level of PXR action in addition to the direct transactivation of protein-coding genes. PXR expression is further controlled by several transcription factors (cross-regulation) giving rise to different PXR transcript variants. Controversies remain regarding the suggested role of feedback regulation (auto-regulation) of PXR expression. In this review, we comprehensively summarize the miRNA-mediated, lncRNA-mediated and transcriptional regulation of PXR expression, and we propose that deciphering the precise mechanisms of PXR expression may bridge our knowledge gap in inter-individual differences in drug metabolism and toxicity.
Identifiants
pubmed: 33164107
doi: 10.1007/s00204-020-02916-x
pii: 10.1007/s00204-020-02916-x
doi:
Substances chimiques
MicroRNAs
0
NR1I2 protein, human
0
Pregnane X Receptor
0
RNA, Long Noncoding
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
11-25Références
Aouabdi S, Gibson G, Plant N (2006) Transcriptional regulation of the PXR gene: identification and characterization of a functional peroxisome proliferator-activated receptor alpha binding site within the proximal promoter of PXR. Drug Metab Dispos 34(1):138–144. https://doi.org/10.1124/dmd.105.006064
doi: 10.1124/dmd.105.006064
pubmed: 16243957
Ayed-Boussema I, Pascussi JM, Zaied C, Maurel P, Bacha H, Hassen W (2012) Ochratoxin A induces CYP3A4, 2B6, 3A5, 2C9, 1A1, and CYP1A2 gene expression in primary cultured human hepatocytes: a possible activation of nuclear receptors. Drug Chem Toxicol 35(1):71–80. https://doi.org/10.3109/01480545.2011.589438
doi: 10.3109/01480545.2011.589438
pubmed: 21834667
Bagamasbad P, Denver RJ (2011) Mechanisms and significance of nuclear receptor auto- and cross-regulation. Gen Comp Endocrinol 170(1):3–17. https://doi.org/10.1016/j.ygcen.2010.03.013
doi: 10.1016/j.ygcen.2010.03.013
pubmed: 20338175
Bailey I, Gibson GG, Plant K, Graham M, Plant N (2011) A PXR-mediated negative feedback loop attenuates the expression of CYP3A in response to the PXR agonist pregnenalone-16alpha-carbonitrile. PLoS ONE 6(2):e16703. https://doi.org/10.1371/journal.pone.0016703
doi: 10.1371/journal.pone.0016703
pubmed: 21311750
pmcid: 3032768
Banerjee M, Robbins D, Chen T (2015) Targeting xenobiotic receptors PXR and CAR in human diseases. Drug Discov Today 20(5):618–628. https://doi.org/10.1016/j.drudis.2014.11.011
doi: 10.1016/j.drudis.2014.11.011
pubmed: 25463033
Benson EA, Eadon MT, Desta Z et al (2016) Rifampin regulation of drug transporters gene expression and the association of microRNAs in human hepatocytes. Front Pharmacol 7:111. https://doi.org/10.3389/fphar.2016.00111
doi: 10.3389/fphar.2016.00111
pubmed: 27199754
pmcid: 4845040
Berthier A, Oger F, Gheeraert C et al (2012) The novel antibacterial compound walrycin A induces human PXR transcriptional activity. Toxicol Sci 127(1):225–235. https://doi.org/10.1093/toxsci/kfs073
doi: 10.1093/toxsci/kfs073
pubmed: 22314385
pmcid: 3435511
Bertilsson G, Heidrich J, Svensson K et al (1998) Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc Natl Acad Sci USA 95(21):12208–12213. https://doi.org/10.1073/pnas.95.21.12208
doi: 10.1073/pnas.95.21.12208
pubmed: 9770465
Blumberg B, Sabbagh W Jr, Juguilon H et al (1998) SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev 12(20):3195–3205. https://doi.org/10.1101/gad.12.20.3195
doi: 10.1101/gad.12.20.3195
pubmed: 9784494
pmcid: 317212
Breuker C, Planque C, Rajabi F et al (2014) Characterization of a novel PXR isoform with potential dominant-negative properties. J Hepatol 61(3):609–616. https://doi.org/10.1016/j.jhep.2014.04.030
doi: 10.1016/j.jhep.2014.04.030
pubmed: 24798619
Brewer CT, Chen T (2016) PXR variants: the impact on drug metabolism and therapeutic responses. Acta Pharm Sin B 6(5):441–449. https://doi.org/10.1016/j.apsb.2016.07.002
doi: 10.1016/j.apsb.2016.07.002
pubmed: 27709012
pmcid: 5045535
Burgess KS, Ipe J, Swart M et al (2018) Variants in the CYP2B6 3′UTR alter in vitro and in vivo CYP2B6 activity: potential role of microRNAs. Clin Pharmacol Ther 104(1):130–138. https://doi.org/10.1002/cpt.892
doi: 10.1002/cpt.892
pubmed: 28960269
Cai Y, Yu X, Hu S, Yu J (2009) A brief review on the mechanisms of miRNA regulation. Genom Proteom Bioinform 7(4):147–154. https://doi.org/10.1016/S1672-0229(08)60044-3
doi: 10.1016/S1672-0229(08)60044-3
Carnahan VE, Redinbo MR (2005) Structure and function of the human nuclear xenobiotic receptor PXR. Curr Drug Metab 6(4):357–367. https://doi.org/10.2174/1389200054633844
doi: 10.2174/1389200054633844
pubmed: 16101574
Chen L, Bao Y, Piekos SC, Zhu K, Zhang L, Zhong XB (2018) A transcriptional regulatory network containing nuclear receptors and long noncoding RNAs controls basal and drug-induced expression of cytochrome P450s in HepaRG cells. Mol Pharmacol 94(1):749–759. https://doi.org/10.1124/mol.118.112235
doi: 10.1124/mol.118.112235
pubmed: 29691280
pmcid: 5988030
Cheng C, Bhardwaj N, Gerstein M (2009) The relationship between the evolution of microRNA targets and the length of their UTRs. BMC Genom 10:431. https://doi.org/10.1186/1471-2164-10-431
doi: 10.1186/1471-2164-10-431
Cloonan N (2015) Re-thinking miRNA-mRNA interactions: intertwining issues confound target discovery. BioEssays 37(4):379–388. https://doi.org/10.1002/bies.201400191
doi: 10.1002/bies.201400191
pubmed: 25683051
pmcid: 4671252
Dempsey JL, Cui JY (2017) Long non-coding RNAs: a novel paradigm for toxicology. Toxicol Sci 155(1):3–21. https://doi.org/10.1093/toxsci/kfw203
doi: 10.1093/toxsci/kfw203
pubmed: 27864543
Dempsey JL, Cui JY (2019) Regulation of hepatic long noncoding RNAs by pregnane X receptor and constitutive androstane receptor agonists in mouse liver. Drug Metab Dispos 47(3):329–339. https://doi.org/10.1124/dmd.118.085142
doi: 10.1124/dmd.118.085142
pubmed: 30593543
pmcid: 6382996
Doricakova A, Vrzal R (2015) A food contaminant ochratoxin A suppresses pregnane X receptor (PXR)-mediated CYP3A4 induction in primary cultures of human hepatocytes. Toxicology 337:72–78. https://doi.org/10.1016/j.tox.2015.08.012
doi: 10.1016/j.tox.2015.08.012
pubmed: 26341324
Dotzlaw H, Leygue E, Watson P, Murphy LC (1999) The human orphan receptor PXR messenger RNA is expressed in both normal and neoplastic breast tissue. Clin Cancer Res 5(8):2103–2107
pubmed: 10473093
Friedman RC, Farh KK, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19(1):92–105. https://doi.org/10.1101/gr.082701.108
doi: 10.1101/gr.082701.108
pubmed: 18955434
pmcid: 2612969
Fukuen S, Fukuda T, Matsuda H et al (2002) Identification of the novel splicing variants for the hPXR in human livers. Biochem Biophys Res Commun 298(3):433–438. https://doi.org/10.1016/s0006-291x(02)02469-5
doi: 10.1016/s0006-291x(02)02469-5
pubmed: 12413960
Gibson GG, Phillips A, Aouabdi S, Plant K, Plant N (2006) Transcriptional regulation of the human pregnane-X receptor. Drug Metab Rev 38(1–2):31–49. https://doi.org/10.1080/03602530600569810
doi: 10.1080/03602530600569810
pubmed: 16684647
Gufford BT, Robarge JD, Eadon MT et al (2018) Rifampin modulation of xeno- and endobiotic conjugating enzyme mRNA expression and associated microRNAs in human hepatocytes. Pharmacol Res Perspect 6(2):e00386. https://doi.org/10.1002/prp2.386
doi: 10.1002/prp2.386
pubmed: 29610665
pmcid: 5869567
Hakkola J, Rysa J, Hukkanen J (2016) Regulation of hepatic energy metabolism by the nuclear receptor PXR. Biochim Biophys Acta 1859(9):1072–1082. https://doi.org/10.1016/j.bbagrm.2016.03.012
doi: 10.1016/j.bbagrm.2016.03.012
pubmed: 27041449
Haslam IS, Jones K, Coleman T, Simmons NL (2008) Rifampin and digoxin induction of MDR1 expression and function in human intestinal (T84) epithelial cells. Br J Pharmacol 154(1):246–255. https://doi.org/10.1038/bjp.2008.69
doi: 10.1038/bjp.2008.69
pubmed: 18332862
pmcid: 2438975
Hukkanen J, Hakkola J, Rysa J (2014) Pregnane X receptor (PXR)—a contributor to the diabetes epidemic? Drug Metabol Drug Interact 29(1):3–15. https://doi.org/10.1515/dmdi-2013-0036
doi: 10.1515/dmdi-2013-0036
pubmed: 24166671
Ihunnah CA, Jiang M, Xie W (2011) Nuclear receptor PXR, transcriptional circuits and metabolic relevance. Biochim Biophys Acta 1812(8):956–963. https://doi.org/10.1016/j.bbadis.2011.01.014
doi: 10.1016/j.bbadis.2011.01.014
pubmed: 21295138
pmcid: 3111845
Iwazaki N, Kobayashi K, Morimoto K et al (2008) Involvement of hepatocyte nuclear factor 4 alpha in transcriptional regulation of the human pregnane X receptor gene in the human liver. Drug Metab Pharmacokinet 23(1):59–66. https://doi.org/10.2133/dmpk.23.59
doi: 10.2133/dmpk.23.59
pubmed: 18305375
Jiang Y, Feng D, Ma X et al (2019) Pregnane X receptor regulates liver size and liver cell fate by yes-associated protein activation in mice. Hepatology 69(1):343–358. https://doi.org/10.1002/hep.30131
doi: 10.1002/hep.30131
pubmed: 30048004
Jilek JL, Tian Y, Yu AM (2017) Effects of microRNA-34a on the pharmacokinetics of cytochrome P450 probe drugs in mice. Drug Metab Dispos 45(5):512–522. https://doi.org/10.1124/dmd.116.074344
doi: 10.1124/dmd.116.074344
pubmed: 28254952
pmcid: 5399649
Kandel BA, Thomas M, Winter S et al (2016) Genomewide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR and PPARalpha in primary human hepatocytes. Biochim Biophys Acta 1859(9):1218–1227. https://doi.org/10.1016/j.bbagrm.2016.03.007
doi: 10.1016/j.bbagrm.2016.03.007
pubmed: 26994748
Kim SW, Md H, Cho M et al (2017) Role of 14-3-3 sigma in over-expression of P-gp by rifampin and paclitaxel stimulation through interaction with PXR. Cell Signal 31:124–134. https://doi.org/10.1016/j.cellsig.2017.01.001
doi: 10.1016/j.cellsig.2017.01.001
pubmed: 28077325
Kliewer SA, Willson TM (2002) Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor. J Lipid Res 43(3):359–364
pubmed: 11893771
Knebel C, Buhrke T, Sussmuth R, Lampen A, Marx-Stoelting P, Braeuning A (2019) Pregnane X receptor mediates steatotic effects of propiconazole and tebuconazole in human liver cell lines. Arch Toxicol 93(5):1311–1322. https://doi.org/10.1007/s00204-019-02445-2
doi: 10.1007/s00204-019-02445-2
pubmed: 30989312
Kozomara A, Griffiths-Jones S (2014) miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 42(Database issue):D68–73. https://doi.org/10.1093/nar/gkt1181
doi: 10.1093/nar/gkt1181
pubmed: 24275495
Kozomara A, Birgaoanu M, Griffiths-Jones S (2019) miRBase: from microRNA sequences to function. Nucleic Acids Res 47(D1):D155–D162. https://doi.org/10.1093/nar/gky1141
doi: 10.1093/nar/gky1141
pubmed: 30423142
Kurose K, Koyano S, Ikeda S, Tohkin M, Hasegawa R, Sawada J (2005) 5' diversity of human hepatic PXR (NR1I2) transcripts and identification of the major transcription initiation site. Mol Cell Biochem 273(1–2):79–85. https://doi.org/10.1007/s11010-005-7757-7
doi: 10.1007/s11010-005-7757-7
pubmed: 16013442
Lamba V, Ghodke Y, Guan W, Tracy TS (2014) microRNA-34a is associated with expression of key hepatic transcription factors and cytochromes P450. Biochem Biophys Res Commun 445(2):404–411. https://doi.org/10.1016/j.bbrc.2014.02.024
doi: 10.1016/j.bbrc.2014.02.024
pubmed: 24530915
pmcid: 4321730
Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854. https://doi.org/10.1016/0092-8674(93)90529-y
doi: 10.1016/0092-8674(93)90529-y
Lee EJ, Baek M, Gusev Y, Brackett DJ, Nuovo GJ, Schmittgen TD (2008) Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors. RNA 14(1):35–42. https://doi.org/10.1261/rna.804508
doi: 10.1261/rna.804508
pubmed: 18025253
pmcid: 2151027
Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA (1998) The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest 102(5):1016–1023. https://doi.org/10.1172/JCI3703
doi: 10.1172/JCI3703
pubmed: 9727070
pmcid: 508967
Li J, Zhang Y (2019) Current experimental strategies for intracellular target identification of microRNA. ExRNA. https://doi.org/10.1186/s41544-018-0002-9
doi: 10.1186/s41544-018-0002-9
Li J, Wang Y, Wang L et al (2016) Identification of rifampin-regulated functional modules and related microRNAs in human hepatocytes based on the protein interaction network. BMC Genom 17(Suppl 7):517. https://doi.org/10.1186/s12864-016-2909-6
doi: 10.1186/s12864-016-2909-6
Li J, Zhao J, Wang H et al (2018) MicroRNA-140-3p enhances the sensitivity of hepatocellular carcinoma cells to sorafenib by targeting pregnenolone X receptor. Onco Targets Ther 11:5885–5894. https://doi.org/10.2147/OTT.S179509
doi: 10.2147/OTT.S179509
pubmed: 30271172
pmcid: 6149869
Li D, Tolleson WH, Yu D et al (2019) Regulation of cytochrome P450 expression by microRNAs and long noncoding RNAs: epigenetic mechanisms in environmental toxicology and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 37(3):180–214. https://doi.org/10.1080/10590501.2019.1639481
doi: 10.1080/10590501.2019.1639481
pubmed: 31305208
pmcid: 6737535
Li D, Wu L, Knox B et al (2020) Long noncoding RNA LINC00844-mediated molecular network regulates expression of drug metabolizing enzymes and nuclear receptors in human liver cells. Arch Toxicol. https://doi.org/10.1007/s00204-020-02706-5
doi: 10.1007/s00204-020-02706-5
pubmed: 33159582
pmcid: 7773225
Maglich JM, Stoltz CM, Goodwin B, Hawkins-Brown D, Moore JT, Kliewer SA (2002) Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Mol Pharmacol 62(3):638–646. https://doi.org/10.1124/mol.62.3.638
doi: 10.1124/mol.62.3.638
pubmed: 12181440
Marx-Stoelting P, Knebel C, Braeuning A (2020) The Connection of azole fungicides with xeno-sensing nuclear receptors, drug metabolism and hepatotoxicity. Cells. https://doi.org/10.3390/cells9051192
doi: 10.3390/cells9051192
pubmed: 32403288
pmcid: 7290820
McDonnell AM, Dang CH (2013) Basic review of the cytochrome p450 system. J Adv Pract Oncol 4(4):263–268. https://doi.org/10.6004/jadpro.2013.4.4.7
doi: 10.6004/jadpro.2013.4.4.7
pubmed: 25032007
pmcid: 4093435
Miao L, Yao H, Li C et al (2016) A dual inhibition: microRNA-552 suppresses both transcription and translation of cytochrome P450 2E1. Biochim Biophys Acta 1859(4):650–662. https://doi.org/10.1016/j.bbagrm.2016.02.016
doi: 10.1016/j.bbagrm.2016.02.016
pubmed: 26926595
Misawa A, Inoue J, Sugino Y et al (2005) Methylation-associated silencing of the nuclear receptor 1I2 gene in advanced-type neuroblastomas, identified by bacterial artificial chromosome array-based methylated CpG island amplification. Cancer Res 65(22):10233–10242. https://doi.org/10.1158/0008-5472.CAN-05-1073
doi: 10.1158/0008-5472.CAN-05-1073
pubmed: 16288011
Moriya N, Kataoka H, Nishikawa J, Kugawa F (2016) Identification of candidate target Cyp genes for micrornas whose expression is altered by PCN and TCPOBOP, representative ligands of PXR and CAR. Biol Pharm Bull 39(8):1381–1386. https://doi.org/10.1248/bpb.b16-00279
doi: 10.1248/bpb.b16-00279
pubmed: 27237601
Nakajima M, Yokoi T (2011) MicroRNAs from biology to future pharmacotherapy: regulation of cytochrome P450s and nuclear receptors. Pharmacol Ther 131(3):330–337. https://doi.org/10.1016/j.pharmthera.2011.04.009
doi: 10.1016/j.pharmthera.2011.04.009
pubmed: 21565218
Nakano M, Nakajima M (2018) Current knowledge of microRNA-mediated regulation of drug metabolism in humans. Expert Opin Drug Metab Toxicol 14(5):493–504. https://doi.org/10.1080/17425255.2018.1472237
doi: 10.1080/17425255.2018.1472237
pubmed: 29718737
Nakano M, Mohri T, Fukami T et al (2015) Single-nucleotide polymorphisms in cytochrome P450 2E1 (CYP2E1) 3′-untranslated region affect the regulation of CYP2E1 by miR-570. Drug Metab Dispos 43(10):1450–1457. https://doi.org/10.1124/dmd.115.065664
doi: 10.1124/dmd.115.065664
pubmed: 26199425
Nishimura M, Naito S, Yokoi T (2004) Tissue-specific mRNA expression profiles of human nuclear receptor subfamilies. Drug Metab Pharmacokinet 19(2):135–149. https://doi.org/10.2133/dmpk.19.135
doi: 10.2133/dmpk.19.135
pubmed: 15499180
Oda Y, Nakajima M, Tsuneyama K et al (2014) Retinoid X receptor alpha in human liver is regulated by miR-34a. Biochem Pharmacol 90(2):179–187. https://doi.org/10.1016/j.bcp.2014.05.002
doi: 10.1016/j.bcp.2014.05.002
pubmed: 24832862
Oladimeji PO, Chen T (2018) PXR: more than just a master xenobiotic receptor. Mol Pharmacol 93(2):119–127. https://doi.org/10.1124/mol.117.110155
doi: 10.1124/mol.117.110155
pubmed: 29113993
pmcid: 5767680
Oladimeji PO, Wright WC, Wu J, Chen T (2019) RNA interference screen identifies NAA10 as a regulator of PXR transcription. Biochem Pharmacol 160:92–109. https://doi.org/10.1016/j.bcp.2018.12.012
doi: 10.1016/j.bcp.2018.12.012
pubmed: 30566892
Oleson L, von Moltke LL, Greenblatt DJ, Court MH (2010) Identification of polymorphisms in the 3′-untranslated region of the human pregnane X receptor (PXR) gene associated with variability in cytochrome P450 3A (CYP3A) metabolism. Xenobiotica 40(2):146–162. https://doi.org/10.3109/00498250903420243
doi: 10.3109/00498250903420243
pubmed: 20082578
pmcid: 3786868
Pan JJ, Xie XJ, Li X, Chen W (2015) Long non-coding RNAs and drug resistance. Asian Pac J Cancer Prev 16(18):8067–8073. https://doi.org/10.7314/apjcp.2015.16.18.8067
doi: 10.7314/apjcp.2015.16.18.8067
pubmed: 26745040
Pascussi JM, Drocourt L, Fabre JM, Maurel P, Vilarem MJ (2000) Dexamethasone induces pregnane X receptor and retinoid X receptor-alpha expression in human hepatocytes: synergistic increase of CYP3A4 induction by pregnane X receptor activators. Mol Pharmacol 58(2):361–372. https://doi.org/10.1124/mol.58.2.361
doi: 10.1124/mol.58.2.361
pubmed: 10908304
Paul P, Chakraborty A, Sarkar D et al (2018) Interplay between miRNAs and human diseases. J Cell Physiol 233(3):2007–2018. https://doi.org/10.1002/jcp.25854
doi: 10.1002/jcp.25854
pubmed: 28181241
Pavek P (2016) Pregnane X receptor (PXR)-mediated gene repression and cross-talk of PXR with other nuclear receptors via coactivator interactions. Front Pharmacol 7:456. https://doi.org/10.3389/fphar.2016.00456
doi: 10.3389/fphar.2016.00456
pubmed: 27932985
pmcid: 5122737
Pondugula SR, Pavek P, Mani S (2016) Pregnane X receptor and cancer: context-specificity is key. Nucl Receptor Res. https://doi.org/10.11131/2016/101198
doi: 10.11131/2016/101198
pubmed: 27617265
pmcid: 5017004
Portius D, Sobolewski C, Foti M (2017) MicroRNAs-dependent regulation of PPARs in metabolic diseases and cancers. PPAR Res 2017:7058424. https://doi.org/10.1155/2017/7058424
doi: 10.1155/2017/7058424
pubmed: 28167956
pmcid: 5266863
Ramamoorthy A, Li L, Gaedigk A et al (2012) In silico and in vitro identification of microRNAs that regulate hepatic nuclear factor 4alpha expression. Drug Metab Dispos 40(4):726–733. https://doi.org/10.1124/dmd.111.040329
doi: 10.1124/dmd.111.040329
pubmed: 22232426
pmcid: 3310421
Ramamoorthy A, Liu Y, Philips S et al (2013) Regulation of microRNA expression by rifampin in human hepatocytes. Drug Metab Dispos 41(10):1763–1768. https://doi.org/10.1124/dmd.113.052886
doi: 10.1124/dmd.113.052886
pubmed: 23935064
pmcid: 3781376
Rao ZZ, Zhang XW, Ding YL, Yang MY (2017) miR-148a-mediated estrogen-induced cholestasis in intrahepatic cholestasis of pregnancy: Role of PXR/MRP3. PLoS ONE 12(6):e0178702. https://doi.org/10.1371/journal.pone.0178702
doi: 10.1371/journal.pone.0178702
pubmed: 28575098
pmcid: 5457162
Reuter T, Herold-Mende C, Dyckhoff G, Rigalli JP, Weiss J (2019) Functional role of miR-148a in oropharyngeal cancer: influence on pregnane X receptor and P-glycoprotein expression. J Recept Signal Transduct Res 39(5–6):451–459. https://doi.org/10.1080/10799893.2019.1694541
doi: 10.1080/10799893.2019.1694541
pubmed: 31771390
Revathidevi S, Sudesh R, Vaishnavi V et al (2016) Screening for the 3′UTR polymorphism of the PXR gene in South Indian breast cancer patients and its potential role in pharmacogenomics. Asian Pac J Cancer Prev 17(8):3971–3977
pubmed: 27644647
Rieger JK, Klein K, Winter S, Zanger UM (2013) Expression variability of absorption, distribution, metabolism, excretion-related microRNAs in human liver: influence of nongenetic factors and association with gene expression. Drug Metab Dispos 41(10):1752–1762. https://doi.org/10.1124/dmd.113.052126
doi: 10.1124/dmd.113.052126
pubmed: 23733276
Rigoutsos I (2009) New tricks for animal microRNAS: targeting of amino acid coding regions at conserved and nonconserved sites. Cancer Res 69(8):3245–3248. https://doi.org/10.1158/0008-5472.CAN-09-0352
doi: 10.1158/0008-5472.CAN-09-0352
pubmed: 19351814
Sana J, Faltejskova P, Svoboda M, Slaby O (2012) Novel classes of non-coding RNAs and cancer. J Transl Med 10:103. https://doi.org/10.1186/1479-5876-10-103
doi: 10.1186/1479-5876-10-103
pubmed: 22613733
pmcid: 3434024
Shah YM, Ma X, Morimura K, Kim I, Gonzalez FJ (2007) Pregnane X receptor activation ameliorates DSS-induced inflammatory bowel disease via inhibition of NF-kappaB target gene expression. Am J Physiol Gastrointest Liver Physiol 292(4):G1114–G1122. https://doi.org/10.1152/ajpgi.00528.2006
doi: 10.1152/ajpgi.00528.2006
pubmed: 17170021
Sharma D, Turkistani AA, Chang W, Hu C, Xu Z, Chang TKH (2017) Negative regulation of human pregnane X receptor by microRNA-18a-5p: evidence for suppression of microRNA-18a-5p expression by rifampin and rilpivirine. Mol Pharmacol 92(1):48–56. https://doi.org/10.1124/mol.116.107003
doi: 10.1124/mol.116.107003
pubmed: 28408657
Smutny T, Mani S, Pavek P (2013) Post-translational and post-transcriptional modifications of pregnane X receptor (PXR) in regulation of the cytochrome P450 superfamily. Curr Drug Metab 14(10):1059–1069. https://doi.org/10.2174/1389200214666131211153307
doi: 10.2174/1389200214666131211153307
pubmed: 24329114
pmcid: 3914715
Smutny T, Duintjer Tebbens J, Pavek P (2015) Bioinformatic analysis of miRNAs targeting the key nuclear receptors regulating CYP3A4 gene expression: The challenge of the CYP3A4 "missing heritability" enigma. J Appl Biomed 13(3):181–188. https://doi.org/10.1016/j.jab.2015.04.002
doi: 10.1016/j.jab.2015.04.002
Smutny T, Dusek J, Hyrsova L et al (2020) The 3′-untranslated region contributes to the pregnane X receptor (PXR) expression down-regulation by PXR ligands and up-regulation by glucocorticoids. Acta Pharm Sin B 10(1):136–152. https://doi.org/10.1016/j.apsb.2019.09.010
doi: 10.1016/j.apsb.2019.09.010
pubmed: 31998607
Swart M, Dandara C (2014) Genetic variation in the 3′-UTR of CYP1A2, CYP2B6, CYP2D6, CYP3A4, NR1I2, and UGT2B7: potential effects on regulation by microRNA and pharmacogenomics relevance. Front Genet 5:167. https://doi.org/10.3389/fgene.2014.00167
doi: 10.3389/fgene.2014.00167
pubmed: 24926315
pmcid: 4044583
Swart M, Dandara C (2019) MicroRNA mediated changes in drug metabolism and target gene expression by efavirenz and rifampicin in vitro: clinical implications. OMICS 23(10):496–507. https://doi.org/10.1089/omi.2019.0122
doi: 10.1089/omi.2019.0122
pubmed: 31526233
pmcid: 6806364
Takagi S, Nakajima M, Mohri T, Yokoi T (2008) Post-transcriptional regulation of human pregnane X receptor by micro-RNA affects the expression of cytochrome P450 3A4. J Biol Chem 283(15):9674–9680. https://doi.org/10.1074/jbc.M709382200
doi: 10.1074/jbc.M709382200
pubmed: 18268015
Takahashi K, Tatsumi N, Fukami T, Yokoi T, Nakajima M (2014) Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet 29(4):333–340. https://doi.org/10.2133/dmpk.dmpk-13-rg-114
doi: 10.2133/dmpk.dmpk-13-rg-114
pubmed: 24552687
Tompkins LM, Sit TL, Wallace AD (2008) Unique transcription start sites and distinct promoter regions differentiate the pregnane X receptor (PXR) isoforms PXR 1 and PXR 2. Drug Metab Dispos 36(5):923–929. https://doi.org/10.1124/dmd.107.018317
doi: 10.1124/dmd.107.018317
pubmed: 18276839
Uno Y, Sakamoto Y, Yoshida K et al (2003) Characterization of six base pair deletion in the putative HNF1-binding site of human PXR promoter. J Hum Genet 48(11):594–597. https://doi.org/10.1007/s10038-003-0076-5
doi: 10.1007/s10038-003-0076-5
pubmed: 14586772
Vachirayonstien T, Yan B (2016) 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. Biochim Biophys Acta 1859(9):1238–1244. https://doi.org/10.1016/j.bbagrm.2016.03.016
doi: 10.1016/j.bbagrm.2016.03.016
pubmed: 27085140
Wang J, Dai S, Guo Y, Xie W, Zhai Y (2014) Biology of PXR: role in drug-hormone interactions. EXCLI J 13:728–739
pubmed: 26417296
pmcid: 4464432
Wang Y, Yu D, Tolleson WH et al (2017) A systematic evaluation of microRNAs in regulating human hepatic CYP2E1. Biochem Pharmacol 138:174–184. https://doi.org/10.1016/j.bcp.2017.04.020
doi: 10.1016/j.bcp.2017.04.020
pubmed: 28438567
pmcid: 5703043
Wang Y, Yan L, Liu J et al (2019) The HNF1alpha-regulated LncRNA HNF1alpha-AS1 is involved in the regulation of cytochrome P450 expression in human liver tissues and Huh7 cells. J Pharmacol Exp Ther 368(3):353–362. https://doi.org/10.1124/jpet.118.252940
doi: 10.1124/jpet.118.252940
pubmed: 30602592
pmcid: 6367688
Wei Z, Chen M, Zhang Y et al (2013) No correlation of hsa-miR-148a with expression of PXR or CYP3A4 in human livers from Chinese Han population. PLoS ONE 8(3):e59141. https://doi.org/10.1371/journal.pone.0059141
doi: 10.1371/journal.pone.0059141
pubmed: 23527115
pmcid: 3604168
Wei Y, Tang C, Sant V, Li S, Poloyac SM, Xie W (2016) A molecular aspect in the regulation of drug metabolism: does PXR-induced enzyme expression always lead to functional changes in drug metabolism? Curr Pharmacol Rep 2(4):187–192. https://doi.org/10.1007/s40495-016-0062-1
doi: 10.1007/s40495-016-0062-1
pubmed: 27795941
pmcid: 5082989
Wu B, Li S, Dong D (2013) 3D structures and ligand specificities of nuclear xenobiotic receptors CAR. PXR and VDR Drug Discov Today 18(11–12):574–581. https://doi.org/10.1016/j.drudis.2013.01.001
doi: 10.1016/j.drudis.2013.01.001
pubmed: 23299080
Xing Y, Yan J, Niu Y (2020) PXR: a center of transcriptional regulation in cancer. Acta Pharm Sin B 10(2):197–206. https://doi.org/10.1016/j.apsb.2019.06.012
doi: 10.1016/j.apsb.2019.06.012
pubmed: 32082968
Yan L, Liu J, Zhao Y et al (2017) Suppression of miR-628-3p and miR-641 is involved in rifampin-mediated CYP3A4 induction in HepaRG cells. Pharmacogenomics 18(1):57–64. https://doi.org/10.2217/pgs-2016-0088
doi: 10.2217/pgs-2016-0088
pubmed: 27967330
Yu D, Green B, Tolleson WH et al (2015) MicroRNA hsa-miR-29a-3p modulates CYP2C19 in human liver cells. Biochem Pharmacol 98(1):215–223. https://doi.org/10.1016/j.bcp.2015.08.094
doi: 10.1016/j.bcp.2015.08.094
pubmed: 26296572
pmcid: 5673105
Yu D, Wu L, Gill P et al (2018) Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol 92(2):845–858. https://doi.org/10.1007/s00204-017-2090-y
doi: 10.1007/s00204-017-2090-y
pubmed: 29067470
Zheng H, Fu R, Wang JT, Liu Q, Chen H, Jiang SW (2013) Advances in the techniques for the prediction of microRNA targets. Int J Mol Sci 14(4):8179–8187. https://doi.org/10.3390/ijms14048179
doi: 10.3390/ijms14048179
pubmed: 23591837
pmcid: 3645737
Zhou C, Tabb MM, Nelson EL et al (2006) Mutual repression between steroid and xenobiotic receptor and NF-kappaB signaling pathways links xenobiotic metabolism and inflammation. J Clin Invest 116(8):2280–2289. https://doi.org/10.1172/JCI26283
doi: 10.1172/JCI26283
pubmed: 16841097
pmcid: 1501109