Expression analysis and bioinformatics prediction of circrnas in peripheral blood mononuclear cells of epilepsy patients_Journal of Epilepsy

Authors：

MAO Jian ^1,2 ,  SUN Hongying ² , ZHANG Shuya ¹ , MENG Chengxi ¹

1. Baotou Medical College of Inner Mongolia University of Science & Technology, Baotou 014040, China;
2. Department of Neurology, the First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science & Technology, Baotou 014010, China;

Corresponding?author：

SUN Hongying, Email: sunhongying2004@sina.com

Keywords：

circular RNA; Epilepsy; Molecular sponge; Bioinformatic

DOI：

10.7507/2096-0247.202112009

Video：

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Objective To study the expression of 4 circular RNA (circRNA) in peripheral blood mononuclear cells (PBMC) of patients with epilepsy and to predict its function by bioinformatics, so as to provide basis for exploring the pathogenesis of epilepsy. Methods From May 2020 to May 2021, 22 epilepsy patients were treated in the Department of Neurology of the First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science and Technology, and 22 control group were selected. There were 13 males and 8 females in the epilepsy group, with an average age of (36.41±8.39)years. There were 11 males and 11 females in the control group, with an average age of (34.41±8.68) years. The expression levels of circRNA EFCAB2, C14orf159, PARG and TMEM39 in PBMC were detected by real-time fluorescence quantitative PCR, and their functions were predicted by bioinformatics. Results Compared with the control group, the relative expression of EFCAB2 and C14orf159 in PBMC of epileptic patients was 1.42±0.06 (t=29.41) and 1.31±0.03 (t=25.27), PARG and TMEM39 were not detected in peripheral blood PBMC. Bioinformatics analysis showed that three mirnas obtained by EFCAB2 were miR-6873-3p, miR-6739-3p and miR-7110-3p. Three mirnas were obtained by C14orf159: miR-1180-3p, miR-6501-3p, and miR-3622b-5p. The seizure-related genes were predicted by TargetScan database. EFCAB2: miR-6873-3p met the requirements of 11 downstream genes. A total of 7 downstream genes of miR-6739-3p met the requirements.A total of 14 downstream genes were eligible for miR-7110-3p and a total of 9 downstream genes were eligible for miR-6501-3p. A total of 14 downstream genes were eligible for miR-3622B-5p.miR-1180-3p has a total of 1 downstream genes that meet the requirements. Conclusions Studies have shown that two circrnas, EFCAB2 and C14orf159, may be important biological markers of epilepsy. Through bioinformatics analysis, these two circrnas may act as "molecular sponges" to regulate epilepsy. EFCAB2 has the potential to act as a "molecular sponge" for miR-6873-3p and miR-7110-3p, and it was found that miR-6873-3p and miR-7110-3 share a common downstream target gene MAP1B-which plays a role in epilepsy by regulating voltage-gated sodium channels. C14orf159 can act as a molecular sponge for miR-6501-3p to regulate the expression of CCL3 and play a role in epilepsy.

Citation： MAO Jian, SUN Hongying, ZHANG Shuya, MENG Chengxi. Expression analysis and bioinformatics prediction of circrnas in peripheral blood mononuclear cells of epilepsy patients. Journal of Epilepsy, 2022, 8(2): 127-132. doi: 10.7507/2096-0247.202112009 Copy

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12.	Li Z, Huang C, Bao C, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol, 2015, 22(3): 256-264.
13.	Li S, Hao M, Wu T, et al. Kaempferol alleviates human endothelial cell injury through circNOL12/miR-6873-3p/FRS2 axis. Biomed Pharmacother, 2021, 137: 111419.
14.	Solé L, Wagnon JL, Akin EJ, et al. The MAP1B binding domain of Nav1. 6 Is required for stable expression at the axon initial segment. J Neurosci, 2019, 39(22): 4238-4251.
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1. Russo ME. The pathophysiology of epilepsy. Cornell Vet, 1981, 71: 221-247.
2. Singh A, Trevick S. The epidemiology of global epilepsy. Neurol Clin, 2016, 34(3): 837-847.
3. Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE commission for classification and terminology. Epilepsia, 2017, 58(4): 512-521.
4. Pal DK, Pong AW, Chung WK. Genetic evaluation and counseling for epilepsy. Nat Rev Neurol, 6 (8): 445–453.
5. Li X, Yang L, Chen LL. The biogenesis, functions, and challenges of circular RNAs. Mol Cell, 2018, 71(3): 428-442.
6. Li J, Lin H, Sun Z, et al. High-throughput data of circular RNA profiles in human temporal cortex tissue reveals novel insights into temporal lobe epilepsy. Cell Physiol Biochem, 2018, 45(2): 677-691.
7. Auvin S. A common language of seizures and epilepsies: International League Against Epilepsy 2017 classifications. Dev Med Child Neurol, 2018, 60(4): 329.
8. Wang K, Liu Y, Shi Y, et al. Amomum tsaoko fruit extract exerts anticonvulsant effects through suppression of oxidative stress and neuroinflammation in a pentylenetetrazol kindling model of epilepsy in mice. Saudi J Biol Sci, 2021, 28(8): 4247-4254.
9. Pitkanen A, Lukasiuk K, Dudek FE, et al. Epileptogenesis. Cold Spring Harb Perspect Med, 2015, 5(10): a022822.
10. L?scher W, Potschka H, Sisodiya SM, et al. Drug resistance in epilepsy: clinical impact, potential mechanisms, and new innovative treatment options. Pharmacol Rev, 2020, 72: 606-638.
11. You X, Vlatkovic I, Babic A, et al. Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci, 2015, 18(4): 603-610.
12. Li Z, Huang C, Bao C, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol, 2015, 22(3): 256-264.
13. Li S, Hao M, Wu T, et al. Kaempferol alleviates human endothelial cell injury through circNOL12/miR-6873-3p/FRS2 axis. Biomed Pharmacother, 2021, 137: 111419.
14. Solé L, Wagnon JL, Akin EJ, et al. The MAP1B binding domain of Nav1. 6 Is required for stable expression at the axon initial segment. J Neurosci, 2019, 39(22): 4238-4251.
15. Thomson DW, Dinger ME. Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet, 2016, 17(5): 272-283.

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Expression analysis and bioinformatics prediction of circrnas in peripheral blood mononuclear cells of epilepsy patients

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