Comprehensive Circular RNA Profiling Reveals the Regulatory Role of the CircRNA-0067835/miR-155 Pathway in Temporal Lobe Epilepsy

Abstract

Background/Aims: Temporal lobe epilepsy (TLE) is the most common form of adult localization-related epilepsy that is accompanied by progressive etiopathology and high incidences of drug resistance. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression, however, the expression profile and clinical significance of circRNAs in TLE remains unknown. Methods: Circular RNA microarray was conducted to identify TLE-related circRNAs. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in TLE in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in TLE cell. Results: 586 differentially expressed circRNAs were identified between TLE and the control tissues. The expression of circRNA-0067835 was significantly down-regulated in tissues and plasma from TLE patients. Lower circRNA-0067835 correlated to increased seizure frequency, HS, and higher Engel’s score. Overexpression of circRNA-0067835 observably decreased SH-SY5Y cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay. Conclusion: Our experiments showed that circRNA-0067835 regulated refractory epilepsy progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with TLE.

A systems approach delivers a functional microRNA catalog and expanded targets for seizure suppression in temporal lobe epilepsy

“…S4). Another mechanism by which miRNA function can be reduced is via circular RNA (circRNA), which binds specific miRNAs rendering the bound miRNAs inactive, and studies have found circRNA levels to be altered in epilepsy (66). Adjustment of criteria for selecting miRNAs could yield additional miRNAs for functional studies.…”

Circular RNA expression profile in blood according to ischemic stroke etiology

“…Indeed, previous reports suggesting the potential role of circRNAs as biomarkers or therapeutic targets in neurological conditions, such as multiple sclerosis or epilepsy, have been already published [29][30][31]. In the stroke field, a number of changes in circRNAs expression levels have been recently described.…”

Profiling and functional analysis of differentially expressed circular RNAs in high glucose‐induced human umbilical vein endothelial cells

“…Circular RNAs identified in humans, animals, plants (including Arabidopsis, rice, and soybean), and yeasts (Saccharomyces cerevisiae and Schizosaccharomyces pombe) [31][32][33][34][35] can serve as sponges of miR-NAs and regulate the expression of parental genes [14,22,36,37]. The roles of circRNAs have been reported in various diseases including diabetes and many vascular diseases [38,39]. Particularly, some studies have identified the functions of certain circRNAs in vascular endothelial cells induced by hypoxia or other inducers [40][41][42].…”