Regulative effects of miR-150 on CYP3A4

doi:10.12092/j.issn.1009-2501.2018.07.005

Abstract

Abstract:

AIM: To explore the role of miR-150 in the regulation of CYP3A4 and the underlying mechanism. METHODS: CYP3A4 mRNA and protein expression were tested by RT-PCR and Western blot when the Chang liver cells were stimulated by FFA containing fatty acids free 1% BSA. Bioinformatics miRNA databases were used to identify CYP3A4-related miRNAs and the wild-type CYP3A4 3′-UTR plasmids were constructed, miR-150 and reporter plasmid were co-transfected into the Chang liver cells to test the expression ratio of the reported fluorescence and the correction fluorescence. Then the miR-150 mimic were transfected into the Chang liver cells, while miRNA inhibitor were transfected into the steatosis cells. RT-PCR and Western blot were used to detect CYP3A4 mRNA and protein expression. RESULTS: The CYP3A4 mRNA and protein level were statistically significantly decreased（P<0.05）, while the mature miR-150 levels were increased (P<0.05）when the Chang liver cells were stimulated after 24 h by 1 mmol/L FFA. CYP3A4 was found to be the target gene of miR-150 with a bioinformatics analysis. Then CYP3A4 mRNA level was significantly decreased (P<0.05). Meanwhile, the expression level of CYP3A4 protein also decreased when the miR-150 mimic were transfected into the Chang liver cells. But CYP3A4 mRNA expression has no statistical significance (P=0.071) in miR-150 inhibitor group. CONCLUSION: The miR-150 can combine with CYP3A4 3′-UTR directly, and can further regulate the expression of CYP3A4 mRNA.

Key words: miR-150, CYP3A4, regulation

CLC Number:

R965.2

LIU Li, PENG Jinfu, GUO Chengxian, YANG Xiding, LI Haigang, YANG Guoping. Regulative effects of miR-150 on CYP3A4[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(7): 749-754.

References

［1］Wojnowski L, Kamdem LK. Clinical implications of CYP3A polymorphisms［J］. Expert Opin Drug Metab Toxicol, 2006, 2(2): 171-182.

［2］Thervet E, Legendre C, Beaune P, et al. Cytochrome P450 3A polymorphisms and immunosuppressive drugs: an update［J］. Pharmacogenomics, 2007, 8(7): 835-849.

［3］Bartel DP. MicroRNAs: target recognition and regulatory functions［J］. Cell, 2009, 136(2): 215-233.

［4］Shukla GC, Singh J. MicroRNAs: processing, maturation, target recognition and regulatory functions［J］. Mol Cell Pharmacol, 2011, 3(3): 83-92.

［5］Peng JF, Liu L, Guo CX, et al. Role of miR-511 in the regulation of OATP1B1 expression by free fatty acid［J］. Biomol Ther (Seoul), 2015, 23 (5): 400-406.

［6］Schmiedlin-Ren P, Thummel KE, Fisher JM, et al. Induction of CYP3A4 by 1 alpha,25-dihydroxyvitamin D3 is human cell line-specific and is unlikely to involve pregnane X receptor［J］. Drug Metab Dispos, 2001, 29 (11): 1446-1453.

［7］Matsubara T, Yoshinari K, Aoyama K, et al. Role of vitamin D receptor in the lithocholic acid-mediated CYP3A induction in vitro and in vivo［J］. Drug Metab Dispos, 2008, 36 (10): 2058-2063.

［8］Wang K, Chen S, Xie W, et al. Retinoids induce cytochrome P450 3A4 through RXR/VDR-mediated pathway［J］. Biochem Pharmacol, 2008, 75 (11): 2204-2013.

［9］Hatziapostolou M, Polytarchou C, Aggelidou E, et al. An HNF4α-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis［J］. Cell, 2011, 147(6): 1233-1247.

［10］Pan YZ, Gao W, Yu AM. MicroRNAs regulate CYP3A4 expression via direct and indirect targeting［J］. Drug Metab Dispos, 2009, 37(10): 2112-2117.

［11］Takagi S, Nakajima M, Mohri T, et al. Post-transcriptional regulation of human pregnane X receptor by micro-RNA affects the expression of cytochrome P450 3A4［J］. J Biol Chem, 2008, 283(15): 9674-9680.

［12］Wei ZL, Chen M, Zhang Y, et al. No correlation of hsa-miR-148a with expression of PXR or CYP3A4 in human livers from Chinese han population［J］. PLoS One, 2013, 8(3): e59141.

［13］Wei Z, Jiang S, Zhang Y, et al. The effect of microRNAs in the regulation of humanCYP3A4: a systematic study using a mathematical model［J］. Sci Rep, 2014 Mar, 4: 4283.

［14］Donato MT. Potential impact of steatosis on cytochrome P450 enzymes of human hepatocytes isolated from fatty liver grafts［J］. Drug Metab Dispos, 2006, 34(9): 1556-1562.

［15］Yoshinari K. Hepatic CYP3A expression is attenuated in obese mice fed a high-fat diet［J］. Pharm Res, 2006, 23(6): 1188-1200.

［16］Gomez-Lechon MJ, Jover R. Cytochrome p450 and steatosis［J］. Curr Drug Metab, 2009, 10(7): 692-699.

［17］Celikbilek M,Baskol M,Taheri S,et al.Circulating microRNAs in patients with non-alcoholic fatty liver disease［J］.World J Hepato,2014,6(8):613-620.

［18］Yamada H, Suzuki K, Ichino N, et al. Associations between circulating microRNAs (miR-21, miR-34a, miR-122 and miR-451) and non-alcoholic fatty liver［J］. Clin Chim Acta, 2013, 424: 99-103.

［19］Cheung O, Puri P, Eicken C, et al. nonalcoholic steatohepatitis is associated with altered hepatic Microrna expression［J］. Hepatology, 2008, 48(6): 1810-1820.

［20］Estep M, Armistead D, Hossain N, et al. Differential expression of miRNAs in the visceral adipose tissue of patients with non-alcoholic fatty liver disease［J］. Aliment Pharmacol Ther, 2010, 32(3): 487-497.

［21］Pogribny IP, Starlard-Davenport A, Tryndyak VP, et al. Difference in expression of hepatic microRNAs miR-29c, miR-34a,miR-155,and miR-200b is associated with strain-specific susceptibility to dietary nonalcoholic steatohepatitis in mice［J］. Lab Invest, 2010, 90(10): 1437-1446.

［22］Jin X, Chen YP, Kong M, et al. Transition from hepatic steatosis to steatohepatitis: unique microRNA patterns and potential downstream functions and pathways［J］. J Gastroenterol Hepatol, 2012, 27(2): 331-340.

［23］Gao Q, Wang XY, Zhou J, et al. Cell line misidentification: the case of the chang liver cell line［J］. Hepatology, 2011, 54: 1894-1895.

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