Discovery of novel human long‐noncoding RNAs (lncRNAs) associated with inflammation

Abstract

Noncoding RNAs are emerging class of transcripts which appear to play critical roles in various cellular processes including cell signaling and metabolism. Recent studies from our laboratory demonstrate that, long noncoding RNA (lncRNA) HOTAIR, which is well‐known as a transcriptional repressor, regulates cytokine expression, glucose metabolism during inflammation in macrophages via regulation of NF‐kB activation. Recently, to identify, lncRNAs that are associated with inflammation and immune signaling, we stimulated human monocyte (THP1 cells) derived macrophage with lipopolysaccharide (LPS) and analyzed the global transcriptome expression using RNAseq analysis. These studies demonstrated that, along with inflammatory protein coding genes and cytokines, a series of lncRNA expressions were significantly induced upon LPS‐stimulation of macrophages, suggesting their potential roles in inflammation and immune signaling. We termed these lncRNAs as LinfRNAs (Long‐noncoding inflammation associated RNA). Importantly, many of these hLinfRNA (human LinfRNAs) expression are also induced by live E.coli exposure, further suggesting their roles in inflammation and immune response. Application of NF‐kB signaling inhibitor suppressed the expression of most hLinfRNAs (LinfRNAs in Human), suggesting their potential regulation via NF‐kB signaling. The structure function of most these hLinfRNAs remains unknown and we are in the process of functional characterization of selected hLinfRNAs (such as hLinfRNA1) in inflammation and immune signaling in human. Understanding their function may help in early diagnosis and can be the key to potential therapeutic target for several inflammation associated diseases, including cardiovascular disease, autoimmune diseases, obesity, diabetes, inflammatory bowel disease, and cancer.