Redondoviridae infection regulates circRNAome in periodontitis

Redondoviridae is a recently identified family of DNA viruses associated with periodontitis. Circular RNAs (circRNAs) are novel endogenous, conserved noncoding RNAs contributing to the virus-related immune-inflammatory response. This study aimed to analyze the expression profiles of circRNAs in the gingival tissues of periodontitis patients with and without Redondoviridae-infection and healthy controls using high-throughput RNA sequencing combined with experimental validation. Out of 17 819 circRNAs, 175 were dysregulated. Functional annotation and enrichment analysis of the differential circRNA host genes demonstrated potential alterations in the molecular and cellular components and metabolism in individuals suffering from periodontitis with Redondoviridae infection. Moreover, "axon guidance," "lysine biosynthesis," and "vascular endothelial growth factor signaling pathways" 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 identified by constructing circRNA-micro RNA (miRNA)-messenger RNA (mRNA) networks. Bioinformatics analyses demonstrated that abnormally expressed circRNAs might contribute to the etiopathogenesis and development of Redondoviridae-related periodontitis. This study's findings have enhanced the current understanding of the Redondoviridae-related periodontitis mechanism and provide insights into further applications for diagnostic markers and therapeutic uses.