{"title":"LncRNA NONHSAT042241 inhibits rheumatoid synovial proliferation, inflammation and aggression via inactivating WNT/β-catenin signaling pathway.","authors":"Yehua Jin, Cen Chang, Xinpeng Zhou, Runrun Zhang, Ping Jiang, Kai Wei, Linshuai Xu, Yiming Shi, Guizhen Yang, Xinliang Lv, Yuejuan Zheng, Dongyi He","doi":"10.1080/08916934.2024.2387076","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This study aims to explore the effect of NONHSAT042241 on the function of rheumatoid arthritis -fibroblast-like synoviocyte (RA-FLS) and the underlying mechanisms.</p><p><strong>Methods: </strong>RA-FLS was treated with NONHSAT042241 overexpression and NONHSAT042241 knockdown lentiviruses. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, Transwell assay, western-blot, ELISA, and qRT-PCR were used to measure the changes of cell proliferation, apoptosis, invasion, secretion of inflammatory cytokines and matrix metalloproteinases (MMPs). Fluorescent <i>in situ</i> hybridization (FISH) assay, RNA pull-down assay, mass spectrometry (MS) and RNA immunoprecipitation (RIP) were used to find the target proteins that bond to NONHSAT042241, and western-blot was used to detect the expression of related proteins of Wnt/β-catenin signaling pathway.</p><p><strong>Results: </strong>Overexpression of NONHSAT042241 inhibited the proliferation of RA-FLS (<i>p</i> < 0.05), invasion, secretion of pro-inflammatory factors (IL-1and IL-6) and MMPs (MMP-1 and MMP-3) (<i>p</i> < 0.05), and elevated the level of pro-apoptotic factors (Bax and cleaved caspase3), while NONHSAT042241 knockdown had the opposite effect. NONHSAT042241 can directly bind to hnRNP D, and down-regulated the expression of β-catenin (<i>p</i> < 0.05), p-GSK-3β (<i>p</i> < 0.05), Cyclin D1 (<i>p</i> < 0.05), PCNA (<i>p</i> < 0.05), and thus reduced the cell proliferation.</p><p><strong>Conclusion: </strong>NONHSAT042241 may inhibit FLS-mediated rheumatoid synovial proliferation, inflammation and aggression. The underlying mechanisms may be that NONHSAT042241 inhibits the activity of Wnt/β-catenin signaling.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"57 1","pages":"2387076"},"PeriodicalIF":3.3000,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autoimmunity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/08916934.2024.2387076","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/4 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: This study aims to explore the effect of NONHSAT042241 on the function of rheumatoid arthritis -fibroblast-like synoviocyte (RA-FLS) and the underlying mechanisms.
Methods: RA-FLS was treated with NONHSAT042241 overexpression and NONHSAT042241 knockdown lentiviruses. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, Transwell assay, western-blot, ELISA, and qRT-PCR were used to measure the changes of cell proliferation, apoptosis, invasion, secretion of inflammatory cytokines and matrix metalloproteinases (MMPs). Fluorescent in situ hybridization (FISH) assay, RNA pull-down assay, mass spectrometry (MS) and RNA immunoprecipitation (RIP) were used to find the target proteins that bond to NONHSAT042241, and western-blot was used to detect the expression of related proteins of Wnt/β-catenin signaling pathway.
Results: Overexpression of NONHSAT042241 inhibited the proliferation of RA-FLS (p < 0.05), invasion, secretion of pro-inflammatory factors (IL-1and IL-6) and MMPs (MMP-1 and MMP-3) (p < 0.05), and elevated the level of pro-apoptotic factors (Bax and cleaved caspase3), while NONHSAT042241 knockdown had the opposite effect. NONHSAT042241 can directly bind to hnRNP D, and down-regulated the expression of β-catenin (p < 0.05), p-GSK-3β (p < 0.05), Cyclin D1 (p < 0.05), PCNA (p < 0.05), and thus reduced the cell proliferation.
Conclusion: NONHSAT042241 may inhibit FLS-mediated rheumatoid synovial proliferation, inflammation and aggression. The underlying mechanisms may be that NONHSAT042241 inhibits the activity of Wnt/β-catenin signaling.
研究目的本研究旨在探讨NONHSAT042241对类风湿性关节炎纤维母细胞样滑膜细胞（RA-FLS）功能的影响及其内在机制：方法：用NONHSAT042241过表达和NONHSAT042241敲除慢病毒处理RA-FLS。方法：用NONHSAT042241过表达和NONHSAT042241敲除慢病毒处理RA-FLS，采用细胞计数试剂盒-8（CCK-8）检测、集落形成检测、流式细胞术、Transwell检测、Western-blot、ELISA和qRT-PCR检测细胞增殖、凋亡、侵袭、炎性细胞因子和基质金属蛋白酶（MMPs）分泌的变化。荧光原位杂交（FISH）检测、RNA下拉检测、质谱分析（MS）和RNA免疫沉淀（RIP）用于寻找与NONHSAT042241结合的靶蛋白，Western-blot用于检测Wnt/β-catenin信号通路相关蛋白的表达：结果：NONHSAT042241的过表达抑制了RA-FLS的增殖（p p p p p p 结论：NONHSAT042241可能会抑制RA-FLS的增殖：NONHSAT042241可抑制FLS介导的类风湿滑膜增殖、炎症和侵袭。其潜在机制可能是 NONHSAT042241 抑制了 Wnt/β-catenin 信号的活性。
期刊介绍：
Autoimmunity is an international, peer reviewed journal that publishes articles on cell and molecular immunology, immunogenetics, molecular biology and autoimmunity. Current understanding of immunity and autoimmunity is being furthered by the progress in new molecular sciences that has recently been little short of spectacular. In addition to the basic elements and mechanisms of the immune system, Autoimmunity is interested in the cellular and molecular processes associated with systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, type I diabetes, multiple sclerosis and other systemic and organ-specific autoimmune disorders. The journal reflects the immunology areas where scientific progress is most rapid. It is a valuable tool to basic and translational researchers in cell biology, genetics and molecular biology of immunity and autoimmunity.
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