MicroRNA hsa-miR-370-3p suppresses the expression and induction of CYP2D6 by facilitating mRNA degradation

摘要: Cytochrome P450 2D6 (CYP2D6) participates in the metabolism of approximately 20-25% prescribed drugs. Genetic polymorphisms influence expression and/or activity CYP2D6, and inter-individual differences drug activation elimination caused by CYP2D6 genetic variants were reported. However, little is known about potential modulation microRNAs (miRNAs). In current study, using silico prediction stabilities miRNA/mRNA complexes, we screened 38 miRNA candidates that may interact with transcript CYP2D6. An inverse correlation between hsa-miR-370-3p was observed human liver tissue samples. Electrophoretic mobility shift assays confirmed able to directly bind its cognate target within coding region transcript. The transfection mimics into HepG2CYP2D6 cell line, a genetically modified line overexpresses exogenous suppress significantly at both mRNA protein levels. also inhibit endogenous production HepaRG cells. Furthermore, HepaRG, HepG2, Huh7 cells, dexamethasone-induced inhibited mimics. To investigate whether mediated suppression inhibiting translation or promoting degradation, an actinomycin D assay used measure stability transcripts. results indicated facilitated degradation mRNA. addition, proteomics analyses proteins isolated from miRNA/mRNA/protein complex suggested group multifunctional interaction thereby degradation.