Identification of hsa-miR-1275 as a Novel Biomarker Targeting MECP2 for Human Epilepsy of Unknown Etiology
Journal
Molecular therapy. Methods & clinical development
Journal Volume
19
Date Issued
2020-12-11
Author(s)
Zhao, Ye
Lu, Congxia
Wang, Huiling
Lin, Qing
Cai, Liangliang
Meng, Fanrong
Tesfaye, Enque Biniam
Tzeng, Chi-Meng
Abstract
Epilepsy affects around 70 million people worldwide, with a 65% rate of unknown etiology. This rate is known as epilepsy of unknown etiology (EUE). Dysregulation of microRNAs (miRNAs) is recognized to contribute to mental disorders, including epilepsy. However, miRNA dysregulation is poorly understood in EUE. Here, we conducted miRNA expression profiling of EUE by microarray technology and identified 57 pathogenic changed miRNAs with significance. The data and bioinformatic analysis results indicated that among these miRNAs, hsa-microRNA (miR)-1275 was highly associated with neurological disorders. Subsequently, new samples of serum and cerebrospinal fluid were collected for validation of hsa-miR-1275 expression by TaqMan assays. Results show that hsa-miR-1275 in serums of EUE were increased significantly, but in cerebrospinal fluid, the miRNA was decreased. Moreover, the MECP2 gene was selected as a hsa-miR-1275 target based on target prediction tools and gene ontology analysis. Validation of in vitro tests proved that MECP2 expression was specifically inhibited by hsa-miR-1275. Additionally, overexpression of hsa-miR-1275 can elevate expression of nuclear factor κB (NF-κB) and promote cell apoptosis. Taken together, hsa-miR-1275 might represent a novel biomarker targeting MECP2 for human EUE.
Subjects
MECP2; epilepsy of unknown etiology; hsa-miR-1275; hsa-miR-132
SDGs
Type
journal article