FIGURE 3.

IL-6 signal cascade and regulatory lncRNA involved in the process. IL-6-bound IL-6R or sIL-6R forms complexes with membrane protein glycoprotein 130 (gp130), which triggers the JAK/STAT pathway and eventually leads to STAT3 phosphorylation and nuclear translocation. NF-κB is also activated via the (PI3K)-AKT pathway and, together with STAT3, promotes immune cell differentiation and IL-6, IL-8 expression. Throughout the process, lncRNAs such as DANCR, HOTAIR, HOTAIRM1, DILC and MALAT1 are involved in either or both pathways by regulating STAT3 phosphorylation, NF-κB interacting with chromatin or the degradation of IκB. Meanwhile, IL-AS1 can regulate IL-6 expression by sponging miR-149-5p, thus protecting IL-6 mRNA.