{"title":"敲低circ_0025908通过调节mir -650依赖的SCUBE2，抑制成纤维细胞样滑膜细胞的增殖、迁移、侵袭和炎症，同时刺激细胞凋亡。","authors":"Ronghua Wang, Hongbo Li, Yunning Han, Lei Li","doi":"10.1080/08916934.2022.2102164","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Circular RNAs (circRNAs) are demonstrated to play vital roles in human diseases, including rheumatoid arthritis (RA). Therefore, this research aimed to explore the effects of hsa_circRNA_0025908 (circ_0025908) on RA.</p><p><strong>Methods: </strong>RNA expression of circ_0025908, microRNA-650 (miR-650), and Signal peptide-CUBepidermal growth factor-like containing protein 2 (SCUBE2) were assessed by real-time quantitative polymerase chain reaction; protein expression of SCUBE2, apoptosis- and invasion-related proteins was evaluated by western blot assay. Functional assays were performed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide, 5-ethynyl-2'-deoxyuridine, transwell, flow cytometry, and enzyme linked immunosorbent assay assays. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays confirmed the interaction relationship among circ_0025908, miR-650, and SCUBE2.</p><p><strong>Results: </strong>Circ_0025908 was overexpressed in synovial tissues and fibroblast-like synoviocytes (FLS) from RA patients. Inhibition of circ_0025908 repressed proliferation, migration, invasion, inflammation, and cell cycle progression, while induced apoptosis in the FLS isolated from RA patients (FLS-RA), accompanied with increased Bax, cleaved caspase-3 and E-cadherin, but declined Bcl-2, N-cadherin and Vimentin. MiR-650 was a target of circ_0025908, and SCUBE2 was a target for miR-650. Silencing of miR-650 could overturned above effects of circ_0025908 knockdown in FLS-RA, whereas its overexpression could mimic those effects by downregulating SCUBE2. Additionally, SCUBE2 expression could be positively regulated by circ_0025908 and inversely regulated by miR-650. Notably, Pearson's correlation analysis confirmed the linear correlation among circ_0025908, miR-650 and SCUBE2 in these RA tissues.</p><p><strong>Conclusion: </strong>Circ_0025908 inhibition can suppress FLS-RA dysfunctions through targeting miR-650/SCUBE2 axis, suggesting a new potential therapeutic clue for RA patients.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"55 7","pages":"473-484"},"PeriodicalIF":3.3000,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Knockdown of circ_0025908 inhibits proliferation, migration, invasion, and inflammation while stimulates apoptosis in fibroblast-like synoviocytes by regulating miR-650-dependent SCUBE2.\",\"authors\":\"Ronghua Wang, Hongbo Li, Yunning Han, Lei Li\",\"doi\":\"10.1080/08916934.2022.2102164\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Circular RNAs (circRNAs) are demonstrated to play vital roles in human diseases, including rheumatoid arthritis (RA). Therefore, this research aimed to explore the effects of hsa_circRNA_0025908 (circ_0025908) on RA.</p><p><strong>Methods: </strong>RNA expression of circ_0025908, microRNA-650 (miR-650), and Signal peptide-CUBepidermal growth factor-like containing protein 2 (SCUBE2) were assessed by real-time quantitative polymerase chain reaction; protein expression of SCUBE2, apoptosis- and invasion-related proteins was evaluated by western blot assay. Functional assays were performed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide, 5-ethynyl-2'-deoxyuridine, transwell, flow cytometry, and enzyme linked immunosorbent assay assays. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays confirmed the interaction relationship among circ_0025908, miR-650, and SCUBE2.</p><p><strong>Results: </strong>Circ_0025908 was overexpressed in synovial tissues and fibroblast-like synoviocytes (FLS) from RA patients. Inhibition of circ_0025908 repressed proliferation, migration, invasion, inflammation, and cell cycle progression, while induced apoptosis in the FLS isolated from RA patients (FLS-RA), accompanied with increased Bax, cleaved caspase-3 and E-cadherin, but declined Bcl-2, N-cadherin and Vimentin. MiR-650 was a target of circ_0025908, and SCUBE2 was a target for miR-650. Silencing of miR-650 could overturned above effects of circ_0025908 knockdown in FLS-RA, whereas its overexpression could mimic those effects by downregulating SCUBE2. Additionally, SCUBE2 expression could be positively regulated by circ_0025908 and inversely regulated by miR-650. Notably, Pearson's correlation analysis confirmed the linear correlation among circ_0025908, miR-650 and SCUBE2 in these RA tissues.</p><p><strong>Conclusion: </strong>Circ_0025908 inhibition can suppress FLS-RA dysfunctions through targeting miR-650/SCUBE2 axis, suggesting a new potential therapeutic clue for RA patients.</p>\",\"PeriodicalId\":8688,\"journal\":{\"name\":\"Autoimmunity\",\"volume\":\"55 7\",\"pages\":\"473-484\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2022-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Autoimmunity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/08916934.2022.2102164\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/7/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autoimmunity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/08916934.2022.2102164","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/7/29 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Knockdown of circ_0025908 inhibits proliferation, migration, invasion, and inflammation while stimulates apoptosis in fibroblast-like synoviocytes by regulating miR-650-dependent SCUBE2.
Background: Circular RNAs (circRNAs) are demonstrated to play vital roles in human diseases, including rheumatoid arthritis (RA). Therefore, this research aimed to explore the effects of hsa_circRNA_0025908 (circ_0025908) on RA.
Methods: RNA expression of circ_0025908, microRNA-650 (miR-650), and Signal peptide-CUBepidermal growth factor-like containing protein 2 (SCUBE2) were assessed by real-time quantitative polymerase chain reaction; protein expression of SCUBE2, apoptosis- and invasion-related proteins was evaluated by western blot assay. Functional assays were performed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide, 5-ethynyl-2'-deoxyuridine, transwell, flow cytometry, and enzyme linked immunosorbent assay assays. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays confirmed the interaction relationship among circ_0025908, miR-650, and SCUBE2.
Results: Circ_0025908 was overexpressed in synovial tissues and fibroblast-like synoviocytes (FLS) from RA patients. Inhibition of circ_0025908 repressed proliferation, migration, invasion, inflammation, and cell cycle progression, while induced apoptosis in the FLS isolated from RA patients (FLS-RA), accompanied with increased Bax, cleaved caspase-3 and E-cadherin, but declined Bcl-2, N-cadherin and Vimentin. MiR-650 was a target of circ_0025908, and SCUBE2 was a target for miR-650. Silencing of miR-650 could overturned above effects of circ_0025908 knockdown in FLS-RA, whereas its overexpression could mimic those effects by downregulating SCUBE2. Additionally, SCUBE2 expression could be positively regulated by circ_0025908 and inversely regulated by miR-650. Notably, Pearson's correlation analysis confirmed the linear correlation among circ_0025908, miR-650 and SCUBE2 in these RA tissues.
Conclusion: Circ_0025908 inhibition can suppress FLS-RA dysfunctions through targeting miR-650/SCUBE2 axis, suggesting a new potential therapeutic clue for RA patients.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
