Li Jiaxin, Lin Haijun, Sun Zhenrong, Kong Guanyi, Yan Xu, Wang Yujiao, Wang Xiaoxuan, Wen Yanhua, Liu Xiang, Zheng Hongkun, Jia Mei, Shi Zhongfang, Xu Rong, Yang Shaohua, Yuan Fang
Department of Pathophysiology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Biomarker Technologies Corporation, Beijing, China.
Cell Physiol Biochem. 2018;45(2):677-691. doi: 10.1159/000487161. Epub 2018 Jan 31.
BACKGROUND/AIMS: Circular RNAs (circRNAs) are a class of long noncoding RNAs with a closed loop structure that regulate gene expression as microRNA sponges. CircRNAs are more enriched in brain tissue, but knowledge of the role of circRNAs in temporal lobe epilepsy (TLE) has remained limited. This study is the first to identify the global expression profiles and characteristics of circRNAs in human temporal cortex tissue from TLE patients.
Temporal cortices were collected from 17 TLE patients and 17 non-TLE patients. Total RNA was isolated, and high-throughput sequencing was used to profile the transcriptome of dysregulated circRNAs. Quantitative PCR was performed for the validation of changed circRNAs.
In total, 78983 circRNAs, including 15.29% known and 84.71% novel circRNAs, were detected in this study. Intriguingly, 442 circRNAs were differentially expressed between the TLE and non-TLE groups (fold change≥2.0 and FDR≤0.05). Of these circRNAs, 188 were up-regulated, and 254 were down-regulated in the TLE patient group. Eight circRNAs were validated by real-time PCR. Remarkably, circ-EFCAB2 was intensely up-regulated, while circ-DROSHA expression was significantly lower in the TLE group than in the non-TLE group (P<0.05). Bioinformatic analysis revealed that circ-EFCAB2 binds to miR-485-5p to increase the expression level of the ion channel CLCN6, while circ-DROSHA interacts with miR-1252-5p to decrease the expression level of ATP1A2.
The dysregulations of circRNAs may reflect the pathogenesis of TLE and circ-EFCAB2 and circ-DROSHA might be potential therapeutic targets and biomarkers in TLE patients.
背景/目的：环状RNA（circRNAs）是一类具有闭环结构的长链非编码RNA，可作为微小RNA海绵调节基因表达。circRNAs在脑组织中更为丰富，但关于circRNAs在颞叶癫痫（TLE）中的作用的了解仍然有限。本研究首次鉴定了TLE患者人类颞叶皮质组织中circRNAs的整体表达谱和特征。
收集了17例TLE患者和17例非TLE患者的颞叶皮质。分离总RNA，并使用高通量测序对失调的circRNAs转录组进行分析。进行定量PCR以验证circRNAs的变化。
本研究共检测到78983种circRNAs，其中包括15.29%的已知circRNAs和84.71%的新circRNAs。有趣的是，TLE组和非TLE组之间有442种circRNAs差异表达（倍数变化≥2.0且FDR≤0.05）。在这些circRNAs中，TLE患者组中有188种上调，254种下调。通过实时PCR验证了8种circRNAs。值得注意的是，circ-EFCAB2强烈上调，而circ-DROSHA在TLE组中的表达明显低于非TLE组（P<0.05）。生物信息学分析表明，circ-EFCAB2与miR-485-5p结合以增加离子通道CLCN6的表达水平，而circ-DROSHA与miR-1252-5p相互作用以降低ATP1A2的表达水平。
circRNAs的失调可能反映了TLE的发病机制，circ-EFCAB2和circ-DROSHA可能是TLE患者潜在的治疗靶点和生物标志物。
