Department of Endocrinology, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
Outpatient Office, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
Biosci Rep. 2019 Dec 20;39(12). doi: 10.1042/BSR20192009.
It is reported that miR-129-5p plays an important role in various diseases, but its effect on rheumatoid arthritis (RA) and the potential mechanism remain to be clarified. In the present research, we aimed to investigate the effect of miR-129-5p on RA and the special molecular mechanism. First, the expression of miR-129-5p was analyzed in RA patients and RA Fibroblast-like synoviocytes (RA-FLSs) by RT-PCR assay. The cell viability, apoptotic rate and the relative expression of caspase-3 and caspase-8 were measured by CCK-8, Annexin-FITC/propidium iodide (PI) and ELISA, respectively. Luciferase reporter assay was performed to investigate the target of miR-129-5p. The results revealed that the expression of miR-129-5p was down-regulated in RA patients and RA-FLSs. In addition, miR-129-5p inhibited cell proliferation and induced apoptosis of RA-FLS. Furthermore, luciferase reporter assay demonstrated that insulin-like growth factor-1 receptor (IGF-1R) was the direct target of miR-129-5p, and IGF-1R promoted cell proliferation and inhibited apoptosis by activating Src/ERK/Egr-1 signaling. Furthermoremore, the Src/ERK/Egr-1 signaling pathway was suppressed by miR-129-5p. Collectively, the results of the present study suggested that miR-129-5p regulated cell proliferation and apoptosis via IGF-1R/Src/ERK/Egr-1 signaling pathway in RA.
据报道，miR-129-5p 在多种疾病中发挥着重要作用，但它对类风湿关节炎（RA）的影响及其潜在机制仍需阐明。在本研究中，我们旨在探讨 miR-129-5p 对 RA 的影响及其特殊的分子机制。首先，通过 RT-PCR 检测 RA 患者和 RA 成纤维样滑膜细胞（RA-FLSs）中 miR-129-5p 的表达。通过 CCK-8 法、Annexin-FITC/PI 法和 ELISA 分别测定细胞活力、凋亡率以及 caspase-3 和 caspase-8 的相对表达水平。通过荧光素酶报告基因实验研究 miR-129-5p 的靶基因。结果表明，miR-129-5p 在 RA 患者和 RA-FLSs 中的表达下调。此外，miR-129-5p 抑制 RA-FLS 增殖并诱导其凋亡。进一步的荧光素酶报告基因实验表明，胰岛素样生长因子-1 受体（IGF-1R）是 miR-129-5p 的直接靶基因，IGF-1R 通过激活 Src/ERK/Egr-1 信号通路促进细胞增殖并抑制细胞凋亡。此外，miR-129-5p 抑制了 Src/ERK/Egr-1 信号通路。综上所述，本研究结果表明，miR-129-5p 通过 IGF-1R/Src/ERK/Egr-1 信号通路调节 RA 中细胞的增殖和凋亡。
