Redondoviridae infection regulates circRNAome in periodontitis

Redondoviridae is a recently identified family of DNA viruses associated with periodontitis. Circular RNAs (circRNAs) emerged as a novel endogenous, conserved noncoding RNAs, which contributed to the virus related immune‐inflammatory response. However, the characteristics and function of circRNAs in Redondoviridae related periodontal inflammation are not yet understood. The present study aimed to analyze the expression profiles of circRNAs in gingival tissues in periodontitis patients with and without Redondoviridae-infection and healthy controls using high-throughput RNA sequencing combined with experimental validation. Out of 17819 circRNAs, 175 circRNAs were dysregulated. Functional annotation and enrichment analysis of the differential circRNAs host genes demonstrated the potential alteration in the molecular and cellular components and metabolism in individuals suffering from periodontitis with Redondoviridae infection. Moreover, “axon guidance” (PATH:04360), “lysine biosynthesis” (PATH:00300) and “vascular endothelial growth factor signaling pathways” (PATH:04370) were significantly enriched in Redondoviridae infected gingivitis tissues. Furthermore, the key circRNAs (circCOL1A1, circAASS, circPTK2, circATP2B4, circDOCK1, circTTBK2, and circMCTP2) associated with the pathobiology of Redondoviridae related periodontitis were revealed by constructing circRNA-miRNA-mRNA networks. The bioinformatic analyses demonstrated that several abnormal expression circRNAs may contribute to the etiopathogenesis and development of Redondoviridae-related periodontitis. The findings of the present study have enhanced the current understanding of the mechanism of Redondoviridae-related periodontitis process and provide an insight into further applications for diagnostic markers and therapeutic uses.