Identification and characterization of non-coding RNA networks in infected macrophages revealing the pathogenesis of F. nucleatum-associated diseases

Abstract

Background: F. nucleatum, as an important periodontal pathogen, is not only closely associated with the development of periodontitis, but also implicated in systemic diseases. Macrophages may act as an important mediator in the pathogenic process of F. nucleatum infection. As non-coding RNAs (ncRNAs) have attracted extensive attention as important epigenetic regulatory mechanisms recently, we focus on the competing endogenous RNA (ceRNA) regulatory networks to elucidate the pathogenesis of F. nucleatum-associated diseases. Results: We screen abnormally expressed mRNAs, miRNAs, lncRNAs and circRNAs in macrophages after F. nucleatum infection via the whole transcriptome sequencing technology, including 375 mRNAs, 5 miRNAs, 64 lncRNAs, and 180 circRNAs. The accuracy of RNA-seq and microRNA-seq result was further verified by qRT-PCR analysis. GO and KEGG analysis show that the differentially expressed genes were mainly involved in MAPK pathway, Toll-like receptor pathway, NF-κB pathway and apoptosis. KEGG disease analysis reveals that they were closely involved in immune system diseases, cardiovascular disease, cancers, inflammatory bowel disease (IBD) et al. We constructed the underlying lncRNA/circRNA-miRNA-mRNA networks to understand their interaction based on the correlation analysis between the differentially expressed RNAs, and then screen the core non-coding RNAs. In which, AKT2 is controlled by hsa_circ_0078617, hsa_circ_0069227, hsa_circ_0084089, lncRNA NUP210, lncRNA ABCB9, lncRNA DIXDC1, lncRNA ATXN1 and lncRNA XLOC_237387 through miR-150-5p; hsa_circ_0001165, hsa_circ_0008460, hsa_circ_0001118, lncRNA XLOC_237387 and lncRNA ATXN1 were identified as the ceRNAs of hsa-miR-146a-3p and thereby indirectly modulating the expression of MITF. Conclusions: Our data identified promising candidate ncRNAs responsible for regulating immune response in the F. nucleatum-associated diseases, offering new insights regarding the pathogenic mechanism of this pathogen.