Department of Plastic and Reconstructive Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, China.
Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, Hebei Province, China.
Hum Cell. 2023 May;36(3):987-996. doi: 10.1007/s13577-023-00873-y. Epub 2023 Feb 7.
The dysregulation of microRNAs plays a critical role in the development of rheumatoid arthritis (RA). This study aims to explore the functional significance of miR-326 in RA. The RT-qPCR results showed that miR-326 was downregulated in synovial tissues of RA patients and RA fibroblast-like synoviocytes (RA-FLS). We found that miR-326 could target and reduce the expression of inhibitor of DNA binding 1 (Id1). MTT assay and flow cytometry were conducted to explore the biological function of miR-326. Our data revealed that the upregulation of miR-326 suppressed cell proliferation and induced apoptosis in RA-FLS. In collagen-induced arthritis mice, intraarticular injection of lentivirus carrying miR-326 overexpression vectors could reduce the arthritis score and attenuate synovial inflammation and cartilage destruction. We also found that long non-coding RNA-Ewing sarcoma-associated transcript 1 (lncRNA-EWSAT1) was significantly increased in RA synovial tissues and RA-FLS. The RNA immunoprecipitation and RNA pull-down assay indicated that lncRNA-EWSAT1 directly bound and negatively regulated the expression of miR-326. Knockdown of lncRNA-EWSAT1 could upregulate miR-326 expression and attenuate its proliferation inhibition and apoptosis induction effect in RA-FLS. In conclusion, the lncRNA-EWSAT1/miR-326 axis might provide a novel therapeutic target in the treatment of RA.
microRNAs 的失调在类风湿关节炎 (RA) 的发展中起着关键作用。本研究旨在探讨 miR-326 在 RA 中的功能意义。RT-qPCR 结果显示，miR-326 在 RA 患者的滑膜组织和 RA 成纤维样滑膜细胞 (RA-FLS) 中下调。我们发现 miR-326 可以靶向并降低 DNA 结合抑制因子 1 (Id1) 的表达。MTT 测定和流式细胞术用于探索 miR-326 的生物学功能。我们的数据表明，miR-326 的上调抑制了 RA-FLS 的细胞增殖并诱导其凋亡。在胶原诱导性关节炎小鼠中，关节内注射携带 miR-326 过表达载体的慢病毒可以降低关节炎评分并减轻滑膜炎症和软骨破坏。我们还发现，长链非编码 RNA-Ewing 肉瘤相关转录本 1 (lncRNA-EWSAT1) 在 RA 滑膜组织和 RA-FLS 中显著增加。RNA 免疫沉淀和 RNA 下拉实验表明，lncRNA-EWSAT1 直接结合并负调控 miR-326 的表达。lncRNA-EWSAT1 的敲低可以上调 miR-326 的表达，并减轻其对 RA-FLS 的增殖抑制和凋亡诱导作用。总之，lncRNA-EWSAT1/miR-326 轴可能为 RA 的治疗提供新的治疗靶点。
