Department of Rheumatology and Immunology, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, China.
Geriatric Department, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, China.
Bioengineered. 2022 Mar;13(3):4951-4963. doi: 10.1080/21655979.2022.2037854.
It has been reported that long noncoding RNAs (LncRNAs) take part in the progression and occurrence of rheumatoid arthritis (RA). The current work aimed to dig the effect of lncRNA OSER1-AS1 on RA and the associated mechanism. Quantitative real-time polymerase chain reaction (qRT-PCR) was made to decide that OSER1-AS1 was significantly lowly expressed in synovial tissue and serum of RA patients, which was consistent in RA-FLSs cell lines. The result of ROC curve indicated that OSER1-AS1 could be a diagnostic biomarker for RA patients. Cell Counting Kit-8 assay (CCK-8), EdU staining and flow cytometry were performed to explore the effect of OSER1-AS1 on RA-FLSs in vitro. Relative levels of interleukin-1 (IL-1), interleukin-6 (IL-6), matrix metalloproteinases-3 (MMP-3) were detected by ELISA and the result displayed that overexpression of OSER1-AS1 inhibited RA-induced inflammatory production of IL-1, IL-6 and MMP3. Bioinformatics analysis, luciferase reporter, RNA immunoprecipitation assays (RIP) and RNA pull-down assay were conducted to confirm the binding between microRNA-1298-5p (miR-1298-5p) and OSER1-AS1 or E2F transcription factor 1 (E2F1). Mechanistically, OSER1-AS1 serves as a competing endogenous (ceRNA) in RA-FLSs through the sponge of miR-1298-5p and increase in the expression of E2F1. Further restoration experiments revealed that miR-1298-5p mimics and E2F1 silencing could partially reverse the inhibiting effect of OSER1-AS1 overexpression on propagation and apoptosis in RA-FLSs. The results illustrated the biological mechanism of OSER1-AS1/miR-1298-59/E2F1 axis in RA progression. The outcomes indicated that OSER1-AS1 might be adopted as a hopeful diagnostic and therapeutic objective for RA.
据报道，长非编码 RNA（lncRNAs）参与了类风湿关节炎（RA）的进展和发生。本研究旨在挖掘 lncRNA OSER1-AS1 对 RA 的影响及其相关机制。采用实时定量聚合酶链反应（qRT-PCR）检测发现，OSER1-AS1 在 RA 患者的滑膜组织和血清中表达明显降低，在 RA-FLSs 细胞系中也存在一致性。ROC 曲线结果表明，OSER1-AS1 可作为 RA 患者的诊断生物标志物。细胞计数试剂盒-8（CCK-8）、EdU 染色和流式细胞术用于研究 OSER1-AS1 对 RA-FLSs 的体外作用。酶联免疫吸附试验（ELISA）检测白细胞介素-1（IL-1）、白细胞介素-6（IL-6）、基质金属蛋白酶-3（MMP-3）的相对水平，结果显示 OSER1-AS1 过表达抑制了 RA 诱导的 IL-1、IL-6 和 MMP3 的炎症产生。通过生物信息学分析、荧光素酶报告基因、RNA 免疫沉淀（RIP）和 RNA 下拉实验证实了 microRNA-1298-5p（miR-1298-5p）与 OSER1-AS1 或 E2F 转录因子 1（E2F1）之间的结合。机制上，OSER1-AS1 在 RA-FLSs 中通过海绵吸附 miR-1298-5p 并增加 E2F1 的表达，从而作为 ceRNA 发挥作用。进一步的恢复实验表明，miR-1298-5p 模拟物和 E2F1 沉默可以部分逆转 OSER1-AS1 过表达对 RA-FLSs 增殖和凋亡的抑制作用。该结果说明了 OSER1-AS1/miR-1298-5p/E2F1 轴在 RA 进展中的生物学机制。研究结果表明，OSER1-AS1 可能成为 RA 有希望的诊断和治疗靶点。
