Ye Shi1,2, Yichen Liu1,2, Zhiyun Wei1,2,3, Yiting Zhang3, Lirong Zhang4, Songshan Jiang5, Yuyu Xiong1,2, Lu Shen1,2, Lin He1,2,3, Qinghe Xing2,3, Shengying Qin2. 1. Bio-X Institutes, Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, PR China. 2. Shanghai Genome Pilot Institutes for Genomics & Human Health, Shanghai 200030, PR China. 3. Children's Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China. 4. Department of Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou 450052, PR China. 5. State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China.
Abstract
AIM: The huge interindividual difference of CYP3A4 expression may contribute to the variability of drug response. Post-transcriptional regulation of CYP3A4 remains elusive although transcriptional regulation has been studied much more clearly. microRNAs (miRNAs) were reported to be one of factors to regulate the expression of CYP3A4 previously. MATERIALS & METHODS: Based on the in silico prediction of 3'-UTR-bindind site of microRNA-27a (miR-27a), the transcriptional and post-transcriptional regulation of miR-27a were investigated through luciferase reporter assay, real-time PCR and immunoblot. RESULTS: The significantly decrease of CYP3A4 3'-UTR-luciferase activity in human embryonic kidney 293 and Hep3B cells was detected after transfected with plasmid that expressed miRNA-27a in luciferase reporter assay. Correlation study was conducted in human livers (n = 26) and significant correlation has been discovered between miRNA-27a and CYP3A4 mRNA and protein level. CONCLUSION: Together, these findings suggest that miR-27a might be involved in the regulation of CYP3A4 gene expression.
AIM: The huge interindividual difference of CYP3A4 expression may contribute to the variability of drug response. Post-transcriptional regulation of CYP3A4 remains elusive although transcriptional regulation has been studied much more clearly. microRNAs (miRNAs) were reported to be one of factors to regulate the expression of CYP3A4 previously. MATERIALS & METHODS: Based on the in silico prediction of 3'-UTR-bindind site of microRNA-27a (miR-27a), the transcriptional and post-transcriptional regulation of miR-27a were investigated through luciferase reporter assay, real-time PCR and immunoblot. RESULTS: The significantly decrease of CYP3A4 3'-UTR-luciferase activity in humanembryonic kidney 293 and Hep3B cells was detected after transfected with plasmid that expressed miRNA-27a in luciferase reporter assay. Correlation study was conducted in human livers (n = 26) and significant correlation has been discovered between miRNA-27a and CYP3A4 mRNA and protein level. CONCLUSION: Together, these findings suggest that miR-27a might be involved in the regulation of CYP3A4 gene expression.
Entities:
Keywords:
CYP3A4; Chinese Han population; miR-27a; microRNA; post-transcriptional regulation
Authors: Dongying Li; William H Tolleson; Dianke Yu; Si Chen; Lei Guo; Wenming Xiao; Weida Tong; Baitang Ning Journal: J Environ Sci Health C Environ Carcinog Ecotoxicol Rev Date: 2019-07-15 Impact factor: 3.781
Authors: Mu-Peng Li; Yao-Dong Hu; Xiao-Lei Hu; Yan-Jiao Zhang; Yong-Long Yang; Chun Jiang; Jie Tang; Xiao-Ping Chen Journal: Int J Environ Res Public Health Date: 2016-11-08 Impact factor: 3.390