Emerging Roles of Long Non-Coding RNAs in Ankylosing Spondylitis

Cytokines play a major role in maintaining lymphocyte homeostasis under both steady-state and inflammatory conditions. Unregulated lymphocytes in steady-state conditions can lead to autoimmunity, whereas during inflammation they can cause excessive tissue damage. Regulatory cytokines function in combination with other environmental signals to properly modulate the function and the extent of lymphocyte activation. Many recent studies have highlighted the importance of regulatory cytokines in controlling the differentiation and function of lymphocytes under steady-state and inflammatory conditions, as well as minimizing tissue damage.

Ankylosing spondylitis (AS), a common type of spondyloarthropathy, is a chronic inflammatory autoimmune disease that mainly affects spine joints, causing severe, chronic pain; additionally, in more advanced cases, it can cause spine fusion. Significant progress in its pathophysiology and treatment has been achieved in the last decade. Immune cells and innate cytokines have been suggested to be crucial in the pathogenesis of AS, especially human leukocyte antigen (HLA)‑B27 and the interleukin‑23/17 axis. However, the pathogenesis of AS remains unclear. The current study reviewed the etiology and pathogenesis of AS, including genome-wide association studies and cytokine pathways. This study also summarized the current pharmaceutical and surgical treatment with a discussion of future potential therapies.

Abstract Objectives Long non‐coding RNAs (lncRNAs) have been demonstrated as crucial regulators in cancer, but whether they are involved in the immune response of cancer cells remains largely undiscovered. GATA3‐AS1 is a novel lncRNA that was upregulated in breast cancer (BC) according to online databases. However, its role in triple‐negative breast cancer (TNBC) was elusive. Methods GATA3‐AS1 expression in BC tissues and adjacent normal tissues was obtained from online databases. Loss‐of‐function assays were designed and conducted to verify the functional role of GATA3‐AS1 in TNBC cells. Bioinformatic analysis and mechanism experiments were applied to explore the downstream molecular mechanism of GATA3‐AS1. Similarly, the upstream mechanism which led to the upregulation of GATA3‐AS1 in TNBC cells was also investigated. Results GATA3‐AS1 was markedly overexpressed in TNBC tissues and cells. Knockdown of GATA3‐AS1 suppressed TNBC cell growth and enhanced the resistance of TNBC cells to immune response. GATA3‐AS1 induced the deubiquitination of PD‐L1 through miR‐676‐3p/COPS5 axis. GATA3‐AS1 destabilized GATA3 protein by promoting GATA3 ubiquitination. Conclusion GATA3‐AS1 contributed to TNBC progression and immune evasion through stabilizing PD‐L1 protein and degrading GATA3 protein, offering a new target for the treatment of TNBC.