title: Aberrant expression of miR-153 is associated with overexpression of hypoxia-inducible factor-1α in refractory epilepsy.
abstract: Evidence suggest that overexpression of hypoxia-inducible factor-1α (HIF-1α) is linked to multidrug resistance of epilepsy. Here we explored whether aberrant expression of HIF-1α is regulated by miRNAs. Genome-wide microRNA expression profiling was performed on temporal cortex resected from mesial temporal lobe epilepsy (mTLE) patients and age-matched controls. miRNAs that are putative regulator of HIF-1α were predicted via target scan and confirmed by real-time quantitative polymerase chain reaction (RT-qPCR). Mimics or miRNA morpholino inhibitors were transfected in astrocytes and luciferase reporter assay was applied to detect HIF-11α expression. Microarray profiling identified down-regulated miR-153 as a putative regulator of HIF-1α in temporal cortex resected from surgical mTLE patients. RT-qPCR confirmed down-regulation of miR-153 in plasma of mTLE patients in an independent validation cohort. Knockdown of miR-153 significantly enhanced expression of HIF-1α while forced expression of miR-153 dramatically inhibited HIF-1α expression in pharmacoresistant astrocyte model. Luciferase assay established that miR-153 might inhibit HIF-1α expression via directly targeting two binding sites in the 3'UTR region of HIF-1α transcript. These data suggest that down-regulation of miR-153 may contribute to enhanced expression of HIF-1α in mTLE and serve as a novel biomarker and treatment target for epilepsy.
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of integrated traditional and western medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan, People's Republic of China.
authors.forename: Peimin
authors.initials: P
authors.lastname: Feng
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000818:Animals; D001253:Astrocytes; D001665:Binding Sites; D016022:Case-Control Studies; D015536:Down-Regulation; D000069279:Drug Resistant Epilepsy / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D051381:Rats; D012307:Risk Factors; D013702:Temporal Lobe / Q000503:physiopathology
chemical_list: D020413:3' Untranslated Regions; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C556500:MIRN153 microRNA, human; D035683:MicroRNAs