ABSTRACT: Periodontitis is an independent risk factor for atherosclerosis, and F. nucleatum is one of the periodontal pathogens. Several studies have confirmed that non-coding RNAs could affect all aspects of AS disease progression, including lipid metabolism, foam cell formation, cell necrosis, etc. However, no studies have explored whether F. nucleatum could affect AS disease progression by regulating non-coding RNAs. In this study, we intend to acquire mRNAs, lncRNAs and circRNAs expression profiles of aorta samples of AS mice from the F. nucleatum group and the Control group by next-generation sequencing(NGS) and perform bioinformatics analysis. Results revealed that 465 mRNA expression were up-regulated and 382 mRNA expression were down-regulated significantly. Some lncRNAs and circRNAs could suppress the binding of miRNA with target genes in post-transcriptional regulation. By integrating with DE-miRNAs-DEGs pairs and screening the common miRNAs, and mRNAs, lncRNAs, circRNAs that have targeted and negatively correlated relationship with the common miRNAs, lncRNA-miRNA-mRNA (including 34 DE-miRNAs, 42 DE-lncRNAs, and 111 DE-mRNAs) and circRNA-miRNA-mRNA (including 19 DE-miRNAs, 49 DE-circRNAs, and 87 DE-mRNAs) regulatory co-expression networks were constructed. GO enrichment analysis was performed on the differentially expressed mRNAs, which were found to be related to molecular functions, biological processes and cellular components such as protein binding, nucleus, postsynaptic dense zone, protein phosphorylation. KEGG analysis showed that they were related to ErbB signaling pathway, neurotrophic factor signaling pathway, glucagon signaling pathway and apoptosis signaling pathway. This suggested that F. nucleatum could promote the development of atherosclerosis through non-coding RNAs network regulation.