Differential Expression and Bioinformatic Analysis of the circRNA Expression in Migraine Patients

Abstract

Background. CircRNAs are noncoding RNA molecules that have recently been described and shown to regulate miRNA functionality. While recent studies have suggested such circRNAs to be associated with pain related diseases in humans, no comprehensive migraine-related circRNA profiles have been generated, and there is currently no clear understanding of whether they can serve as regulators of migraine pathology. Methods. We initially conducted a circRNA microarray analysis of the plasma of migraine patients and healthy controls. Based upon these data, we then selected 8 differentially expressed circRNAs and confirmed their expression in more migraine patient plasma samples via real-time PCR. We then performed functional and pathway enrichment analyses. Lastly, using a robust rank aggregation approach, we constructed a ceRNA network according to predicted circRNA–miRNA and miRNA–mRNA pairs in these migraine patient samples. Results. We were able to detect 2039 circRNAs in our patient samples, with 794 of 1245 these circRNAs being up- and downregulated in migraine patients relative to controls, respectively ( fold change ≥ 1.5 , p < 0.01 ). A qRT-PCR analysis confirmed that the expression of hsa_circRNA_100236, hsa_circRNA_102413, and hsa_circRNA_000367 was significantly enhanced in migraine patients, whereas the expression of hsa_circRNA_103809, hsa_circRNA_103670, and hsa_circRNA_101833 was significantly reduced in these individuals relative to healthy controls. We found these differentially regulated circRNAs to be associated with numerous predicted biological processes, with enrichment analyses suggesting that they may modulate the PI3K-Akt signaling so as to promote inflammation to drive migraine development. However, further research will be needed to formally test these mechanistic possibilities and to validate these circRNAs as potential biomarkers of migraine patients. Conclusions. Our results offer new potential insights into the mechanistic basis of this condition and suggest that hsa_circRNA_000367 and hsa_circRNA_102413 may offer value as regulators of migraine pathology.

Transcriptome analysis of microRNAs, circRNAs, and mRNAs in the dorsal root ganglia of paclitaxel-induced mice with neuropathic pain

“…CircRNAs, a type of non-coding RNAs, can mediate the functions of diverse molecules including non-coding RNAs, mRNAs, DNA, and proteins. Thus, circRNAs play critical roles in tumor genesis and development, in sensitivity to radiation and chemotherapy, and in pain ( Wang et al, 2018 ; Kristensen et al, 2019 ; Zhang et al, 2019 ; Lin et al, 2020 ; Song et al, 2020 ; Zhang H. H. et al, 2020 ). In our present study, we found that 16 circRNAs in the DRG showed altered expression levels in response to treatment using PTX.…”

“…CircRNAs, a type of non-coding RNAs, have been identified as miRNA sponges that regulate the expression and function of coding mRNAs, and are involved in various biological processes including pain (Wang et al, 2018;Lin et al, 2020;Song et al, 2020;Zhang H. H. et al, 2020). From our Bupivacaine (Bv)-induced neural apoptosis↑ ; diabetic peripheral neuropathy (Bali et al, 2021) 10.3389/fnmol.2022.990260 RNA-Seq data, 16 circRNAs were extracted as DEGs induced by treatment using PTX (Figure 3A and Table 5).…”

Expression Profiles and Bioinformatic Analysis of Circular RNAs in Db/Db Mice with Cardiac Fibrosis

“…The lower the P-value is, the more significant the pathway. 16 The recommended P-value cutoff is 0.05.…”

The Epigenetics of Migraine

“…Another possible epigenetic marker significant for migraine could be circRNA. Lin et al identified 794 and 1245 circRNAs, which were increased and decreased, respectively, in migraineurs compared to healthy controls [62]. The authors concluded that hsa_circRNA_103670, hsa_circRNA_103809, hsa_circRNA_000367, and hsa_circRNA_102413 may be closely related to the development of migraine.…”