Yan Liu, Jianjun Yuan, Quan Zhang, Zhishuai Ren, Guang Li, Rong Tian
{"title":"Circ_0016347 modulates proliferation, migration, invasion, cell cycle, and apoptosis of osteosarcoma cells <i>via</i> the miR-661/IL6R axis.","authors":"Yan Liu, Jianjun Yuan, Quan Zhang, Zhishuai Ren, Guang Li, Rong Tian","doi":"10.1080/08916934.2022.2037129","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma is a common primary bone tumour in children and adolescents. Circular RNAs (circRNAs) exert vital functions in human diseases, including osteosarcoma. Therefore, we explored the role of circ_0016347 in osteosarcoma.</p><p><strong>Methods: </strong>The real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of circ_0016347, microRNA-661 (miR-661), and Interleukin-6 receptor (IL6R) in osteosarcoma tissues and cells. The proliferation of osteosarcoma cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and EdU experiments. The migration and invasion were determined by transwell assay. The cell cycle distribution and apoptosis were assessed by flow cytometry assay. The association relationships among circ_0016347, miR-661, and IL6R were analyzed by dual-luciferase reporter assays. The western blot assay was employed to assay the protein expression. A xenograft experiment was established to clarify the functional role of circ_0016347 inhibition <i>in vivo</i>.</p><p><strong>Results: </strong>Circ_0016347 was obviously overexpressed in osteosarcoma tissues and cells compared with control groups. The suppression of circ_0016347 impeded proliferation, migration, invasion, and cell cycle and induced apoptosis in osteosarcoma cells, which was overturned by knockdown of miR-661. Consistently, circ_0016347 knockdown repressed tumour growth <i>in vivo</i>. Moreover, miR-661 directly targeted and inhibited IL6R, and the upregulation of IL6R reversed miR-661-induced effects on osteosarcoma cells. Furthermore, circ_0016347 could regulate IL6R expression through miR-661. Inhibition of circ_0016347 also inactivated the Janus kinase 2 (JAK2)/Transcription 3 (STAT3) signalling pathway in osteosarcoma cells by IL6R.</p><p><strong>Conclusion: </strong>Circ_0016347 functioned as an oncogene in osteosarcoma at least in part by the miR-661/IL6R axis and JAK2/STAT3 signalling pathway.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"55 4","pages":"264-274"},"PeriodicalIF":3.3000,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autoimmunity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/08916934.2022.2037129","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/2/15 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 2
Abstract
Background: Osteosarcoma is a common primary bone tumour in children and adolescents. Circular RNAs (circRNAs) exert vital functions in human diseases, including osteosarcoma. Therefore, we explored the role of circ_0016347 in osteosarcoma.
Methods: The real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of circ_0016347, microRNA-661 (miR-661), and Interleukin-6 receptor (IL6R) in osteosarcoma tissues and cells. The proliferation of osteosarcoma cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and EdU experiments. The migration and invasion were determined by transwell assay. The cell cycle distribution and apoptosis were assessed by flow cytometry assay. The association relationships among circ_0016347, miR-661, and IL6R were analyzed by dual-luciferase reporter assays. The western blot assay was employed to assay the protein expression. A xenograft experiment was established to clarify the functional role of circ_0016347 inhibition in vivo.
Results: Circ_0016347 was obviously overexpressed in osteosarcoma tissues and cells compared with control groups. The suppression of circ_0016347 impeded proliferation, migration, invasion, and cell cycle and induced apoptosis in osteosarcoma cells, which was overturned by knockdown of miR-661. Consistently, circ_0016347 knockdown repressed tumour growth in vivo. Moreover, miR-661 directly targeted and inhibited IL6R, and the upregulation of IL6R reversed miR-661-induced effects on osteosarcoma cells. Furthermore, circ_0016347 could regulate IL6R expression through miR-661. Inhibition of circ_0016347 also inactivated the Janus kinase 2 (JAK2)/Transcription 3 (STAT3) signalling pathway in osteosarcoma cells by IL6R.
Conclusion: Circ_0016347 functioned as an oncogene in osteosarcoma at least in part by the miR-661/IL6R axis and JAK2/STAT3 signalling pathway.
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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