Abstract
Long non-coding RNAs (lncRNAs) have recently emerged as new regulatory molecules with diverse functions in regulating gene expression and significant roles in the immune response. However, the function of many unknown lncRNAs is still unclear. By studying the regulatory effect of daidzein (DA) on immunity, we identified a novel lncRNA with an immune regulatory function: lncRNA- XLOC_098131. In vivo, DA treatment upregulated the expression of lncRNA- XLOC_098131, FOS, and JUN in chickens and affected the expression of activator protein 1 (AP-1) to regulate MAPK signaling, Toll-like receptor signaling, and related mRNA expression. It also enhanced macrophage activity and increased the numbers of blood neutrophils and mononuclear cells, which can improve the body's ability to respond to stress and bacterial and viral infections. Furthermore, DA treatment also reduced B lymphocyte apoptosis and promoted the differentiation of B lymphocytes into plasma cells, which in turn resulted in the production of more immunoglobulins and the promotion of antigen presentation. In vitro, using HEK293FT cells, we demonstrated that mir-548s could bind to and decrease the expression of both FOS and lncRNA- XLOC_098131. LncRNA- XLOC_098131 served as a competitive endogenous RNA to stabilize FOS by competitively binding to miR-548s and thereby reducing its inhibitory effect of FOS expression. Therefore, we concluded that the novel lncRNA XLOC_098131 acts as a key regulatory molecule that can regulate the Toll-like receptor signaling pathway and related immune function by serving as a competitive endogenous RNA to stabilize FOS mRNA expression.
Highlights
As a template RNA molecule, messenger RNA (mRNA) plays an important role in DNA genetic information transmission and protein synthesis [1]
Our results demonstrated that DA supplementation at a dose of 20 mg/kg increased the serum IgA and IgM levels in hens on the 4 and 8th weeks of the experiment, which is consistent with previous research
The DA treatment resulted in an increase in the proliferative responses of B cells, as shown by the changes in the LPS stimulation index (SI) values obtained in vitro using peripheral blood from hens on the 8th week of the experiment, but had no effect on the proliferative responses of T cells, which is consistent with the previous finding that 0.5 mg/kg DA has no significant effect on T lymphocyte proliferative responses in 5- to 6-week-old boars [50]
Summary
As a template RNA molecule, mRNA plays an important role in DNA genetic information transmission and protein synthesis [1]. Long non-coding RNAs (lncRNAs), which are non-coding RNA transcripts that are longer than 200 nucleotides and lack apparent open reading frames, play important roles in many cellular biological processes, including cell cycle progression, apoptosis, development, muscle differentiation, and immune regulation [3], and participate mainly in epigenetic, transcriptional, and posttranscriptional regulation [4]. LncRNAs mediate gene silencing by recruiting chromatin-modifying complexes toward target genes through sequence-specific binding [6]. LncRNAs, such as Kcnq1ot and Air, which map to the Kcnq and Igf2r imprinted gene clusters, respectively, mediate the transcriptional silencing of multiple genes by interacting with chromatin and recruiting the chromatin-modifying machinery [7]. LncRNAs can regulate gene expression as competitive endogenous RNAs (ceRNAs) [5, 9, 10]
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