A-F Song1, L Kang, Y-F Wang, M Wang. 1. Department of Rheumatology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia, P. R. China. mei_wang1980@sina.com.
Abstract
OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Omayma O Abdelaleem; Shereen Rashad Mohammed; Hassan S El Sayed; Sherin Khamis Hussein; Doaa Y Ali; Mostafa Y Abdelwahed; Sylvana N Gaber; Nada F Hemeda; Rehab G Abd El-Hmid Journal: PLoS One Date: 2022-01-06 Impact factor: 3.240