Levels of miR-133 a/b and MRP1 in peripheral blood of patients with drug-refractory epilepsy / 中国病理生理杂志

ABSTRACT

AIM:To investigate the levels and clinical significance of microRNA-133a/b (miR-133a/b) and multidrug resistance-associated protein 1 ( MRP1 ) in peripheral blood of the patients with drug-refractory epilepsy. METHODS:Prediction of the miRNAs targeting transcriptional regulation of MRP1 was conducted by bioinformatics analy-sis.The plasmids containing wild type and mutant 3’UTR of MRP1 reporter gene were constructed.Dual luciferase report-er gene assay was used to verify this prediction.In addition, the peripheral blood samples of the epilepsy patients (37 cases were drug-refractory, the other 58 cases were nonresistant) were collected.The levels of miR-133a/b and MRP1 were measured by real-time PCR and ELISA.RESULTS:Through TargetScan database, it was predicted that miR-133a/b tran-scriptionally regulated MRP1.The results of dual luciferase report gene assay suggested that luciferase activity in experi-mental group with miR-133a/b mimics, pMIR-MRP1 and pRLTK plasmids were down-regulated by 76.9% and 64.1%compared with that in control group with scramble mimic, pMIR-MRP1 and pRLTK plasmids.The luciferase activity was up-regulated by 3.62 times and 2.04 times in mutation group with miR-133a/b mimics, pMIR-mut-MRP1 and pRLTK plasmids compared with experimental group.Before administration, the serum levels of miR-133a/b in the epilepsy patients without drug resistance was 2.18 times and 1.74 times higher than than in the epilepsy patients with drug resistance ( P<0.05), respectively, while MRP1 expression level was 3.72 times higher in the epilepsy patients with drug resistance than those in the epilepsy patients without drug resistance.After administration, the levels of miR-133a/b in the epilepsy pa-tients without drug resistance were 2.76 times and 2.95 times higher than those in the epilepsy patients with drug resistance (P<0.05), respectively, while the serum level of MRP1 in the epilepsy patients with drug resistance was 4.99 times higher than that in the epileptic patients without drug resistance (P<0.01).CONCLUSION:miR-133a/b transcriptio-nally regulates MRP1.There are lower expression levels of miR-133a/b and higher expression level of MRP1 in the epilep-sy patients with drug resistance compared with those in the epilepsy patients without drug resistance.miR-133a/b and MRP1 may be a diagnostic indicator for determining refractory epilepsy.