Abstract Objective: To explore the expression profile of circular RNA (circRNA) in peripheral blood mononuclear cells (PBMCs) of patients with Graves′ disease and its potential diagnostic value. Methods: Five patients with Graves′disease and five healthy controls were selected to analyze the expression profile of circRNA in PBMCs by next generation highthroughput sequencing. Another 40 patients with Graves′ disease and 40 healthy controls were selected to verify the differential expression of circRNA; MicroRNAs (miRNAs) that may bind to differentially expressed circRNA were predicted according to CircInteract database; Bioinformatics was used to analyze the potential biological functions of differentially expressed circRNA; ROC curve analysis of the differential expression of circRNA in Graves′disease. Results: Next generation highthroughput sequencing data showed that, compared with healthy controls, there were 23 215 up-regulated and 13 695 down-regulated circRNA in patients with Graves′disease, of which 669 were significantly differentially expressed, including 360 up-regulated and 309 down regulated circRNA (difference multiple≥2, P≤0.05). Hsa_circ_0114427,hsa_circ_0007470,hsa_circ_0048232 and hsa_circ_0002672 were confirmed by real-time PCR, and the expression level was consistent with that of high-throughput sequencing, and there were statistical significance between the two groups (P<0.01 and P<0.05), but there was no difference in expression of hsa_circ_0039161 and hsa_circ_0002600.GO enrichment analysis showed that the up-regulated circRNA was closely related to polymer metabolism, cell membrane binding organelles, and transferase activation. KEGG analysis showed that the differentially expressed circRNA might be involved in thyroid hormone signaling, phosphatidylinositol signaling system, non-small cell lung cancer and other related signaling pathways. ROC curve showed hsa_circ_0114427 has the biggest area under the curve. Conclusion: There are clearly differentially expressed circular RNAs in PBMCs of patients with Graves′disease. Hsa_circ_0114427 may be related to the occurrence and development of Graves′disease.
[Key words]Graves′disease; circular RNA; nextgeneration high-throughput sequencing; biomarkers; PBMCs
|