Long noncoding RNAs in regulation of inflammation, immune response, and glucose metabolism

Abstract

Noncoding RNAs (ncRNAs) are emerging players in cell signaling and metabolism. Studies from our laboratory demonstrate that long noncoding RNA (lncRNA) HOTAIR plays critical roles in inflammation via regulation of NF‐kB activation and cytokine expression. HOTAIR also regulates glucose metabolism in macrophages during inflammation. Importantly, metabolic reprogramming is critically linked to inflammation and macrophage activation. Therefore, our findings showing the HOTAIR mediated regulation of glucose metabolism in macrophages indicate potential roles of lncRNAs in macrophage activation and metabolic reprogramming. In a recent study, we explored potential involvement of other ncRNAs in inflammation and immune signaling. Based on independent RNAseq analyses in mouse and human macrophages, we have discovered a series novel mouse and human lncRNAs which are potential regulators of cytokine expression, inflammation, and immune response. Notably, there appear to be poor conservation among the lncRNAs between mouse and human. Mechanistic studies demonstrated that some of the novel inflammatory lncRNAs are regulated via NF‐kB pathways while others are not, suggesting distinct modes of action of different lncRNAs during inflammatory response in macrophages. Here, we will present the discovery of novel mouse and human lncRNAs that are potential regulators of inflammation and immune signaling and discuss functional roles of selected lncRNAs in cytokine regulation, inflammation, and glucose metabolism in macrophages.