MiR-34a-5p inhibits fibroblast‑like synoviocytes proliferation via XBP1.

Abstract

Rheumatoid arthritis (RA) is an autoimmune, inflammatory disease mainly manifested by joint damage. Its mechanism is not completely clear at present. Previous studies have found that microRNA-34a-5p (miR-34a-5p) is involved in the development of many inflammatory diseases. In this study, we intended to study the role and mechanism of miR-34a-5p in the development of RA. We predicted that miR-34a-5p could directly inhibit the expression of X-box binding protein 1 (XBP1). We analyzed whether miR-34a-5p could inhibit XBP1 expression by Real-time Quantitative PCR. Cell Counting Kit-8 was used to detect the proliferation of fibroblast‑like synoviocytes (FLS). Tumor Necrosis Factor-α (TNF-α) and interleukin-6 (IL-6) secreted by FLS were measured by Enzyme-Linked Immunosorbent assay. Western blot was used to detect the expression of XBP1 and Luciferase assay was used to verify the interaction between miR-34a-5p and XBP1. We found that miR-34a-5p expression is lower in RA synovial tissue compared to osteoarthritis (OA). Moreover, miR-34a-5p inhibited the proliferation of FLS and inhibited the secretion of TNF-α and IL-6 by FLS. According to the prediction, we found that miR-34a-5p may bind to the 3' untranslated region (3' UTR) of XBP1, thereby inhibiting its expression. Through functional experiments and Luciferase experiments, we showed that miR-34a-5p can directly target XBP1, thereby inhibiting its expression. In short, miR-34a-5p can directly inhibit the expression of XBP1, ultimately inhibit the proliferation of FLS, and inhibit the secretion of TNF-α and IL-6 by FLS. This study can provide new ideas for the treatment of RA.