Evaluation of P-glycoprotein-targeting circulating microRNAs as peripheral biomarkers for medically intractable epilepsy  

作　　者：Yangmei Xie Yiye Shao Xue Gong Ming Wang Yinghui Chen 

机构地区：[1]Department of Neurology,Huashan Hospital,Fudan University,National Center for Neurological Disorders,12 Wulumuqi Road,Shanghai 200040,China [2]Department of Neurology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200940,China [3]Community Health Service Center of Xinqiao Town,Songjiang District,Shanghai 201612,China

出　　处：《Acta Epileptologica》2023年第1期14-24,共11页癫痫学报（英文）

基　　金：This research was supported by grants from the National Natural Science Foundation of China(81971209)to YC;National Natural Science Foundation of China(82101518)to YS;Shanghai Sailing Program(20YF1439400)to YS.

摘　　要：Background Early diagnosis of medically intractable epilepsy is challenging in clinical work.P-glycoprotein(P-gp)is one of the most important multidrug efux transporters,which has been demonstrated to contribute to the drug resistance of intractable epilepsy.The present study was aimed to explore the diagnostic value of microRNAs(miRNAs)targeting P-gp for medically intractable epilepsy.Methods Thirty-six patients with intractable epilepsy and 36 epilepsy patients responsive to anti-epilepsy drugs,who visited Jinshan Hospital of Fudan University from September 2014 to September 2016,were enrolled in this study.Clinical information of the patients was obtained by retrospectively reviewing medical records.MiRNAs with diferential serum expression between the two groups of patients were detected by microarray assay.Meanwhile,miRNAs that were confrmed to regulate P-gp in vitro by western blot were selected for further validation.In the validation phase,reverse transcription quantitative PCR(RT-qPCR)was conducted to confrm the diferential expression of the candidate miRNAs in the epilepsy cohorts.Receiver operating characteristic(ROC)curve analysis was carried out to evaluate the diagnostic value of the miRNAs for intractable epilepsy.Results Three miRNAs including miR-6514-3p,miR-6076-5p,and miR-6855-3p were identifed to be candidate miRNAs by microarray assay.The results of western blotting validated that miR-146a-5p and miR-138-5p could regulate P-gp expression in vitro,so they were included in the candidate miRNAs for further validation.In the validation phase,the results of RT-qPCR indicated that compared with drug-responsive patients,the patients with intractable epilepsy showed decreased level of miR-138-5p and increased level of miR-146a-5p.The results of ROC curve analysis indicated that miR-138-5p(AUC=0.877)and miR-146a-5p(AUC=0.866)had high diagnostic value for intractable epilepsy.In addition,the miR-panel composed of miR-138-5p and miR-146a-5p showed higher diagnostic value(AUC=0.926)than the miRNAs selecte

关 键 词：Intractable epilepsy Drug resistance P-GLYCOPROTEIN Circulating miRNAs BIOMARKER 

分 类 号：R742.1[医药卫生—神经病学与精神病学]