SYSTEMATIC IDENTIFICATION AND ANALYSIS OF EXPRESSION PROFILES OF MRNAS AND INCRNAS IN MACROPHAGE INFLAMMATORY RESPONSE

摘要

Long noncoding RNAs (lncRNAs), once thought to be transcriptional noise, have been recently shown to regulate a variety of biological processes. However, their roles in the inflammatory response are largely unexplored. In this study, we performed high-throughput sequencing to identify the profiles of mRNA and lncRNA transcriptomes in response to lipopolysaccharide (LPS) stimulation, followed by a comprehensive bioinformatics analysis. We found a total of 325 lncRNAs and 1,187 mRNAs to be significantly dysregulated in RAW264.7 cells stimulated with LPS (fold change >4.0 or <0.25, false discovery rate <0.01). Further validation with gRT-PCR demonstrated that Cd40 and Traf1 mRNAs were significantly upregulated, whereas Slc43a2 and Ccnd1 were downregulated in RAW264.7 cells treated with LPS. Gene ontology (GO) analysis indicated that the altered mRNAs and lncRNAs were mainly involved in the immune response, inflammation response, chemokine receptor binding, protein binding, and regulation of cytokine production. KEGG pathway analysis showed that altered lncRNAs and mRNAs were significantly enriched in immune- and inflammation-related signaling pathways, such as Herpes simplex infection, cytokine-cytokine receptor interaction, and TNF, PI3K-Akt, MAPK, NF-kappa B, and JAK-STAT signaling pathways. lncRNA-mRNA network analysis showed that the coexpression network profile for mRNAs and lncRNAs from the immune category consisted of 93 network nodes and 145 connections among 70 differentially expressed mRNAs and 23 dysregulated lncRNAs, suggesting that lncRNAs play an important role in the regulation of functional mRNA expression in LPS-induced inflammation.