{"data":{"id":"10.6084/m9.figshare.c.2031692","type":"dois","attributes":{"doi":"10.6084/m9.figshare.c.2031692","prefix":"10.6084","suffix":"m9.figshare.c.2031692","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Sun, Xiaoxia","givenName":"Xiaoxia","familyName":"Sun","affiliation":[],"nameIdentifiers":[]},{"name":"Zhang, Jian","givenName":"Jian","familyName":"Zhang","affiliation":[],"nameIdentifiers":[]},{"name":"Hou, Zhaohua","givenName":"Zhaohua","familyName":"Hou","affiliation":[],"nameIdentifiers":[]},{"name":"Han, Qiuju","givenName":"Qiuju","familyName":"Han","affiliation":[],"nameIdentifiers":[]},{"name":"Zhang, Cai","givenName":"Cai","familyName":"Zhang","affiliation":[],"nameIdentifiers":[]},{"name":"Tian, Zhigang","givenName":"Zhigang","familyName":"Tian","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"miR-146a is directly regulated by STAT3 in human hepatocellular carcinoma cells and involved in anti-tumor immune suppression"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Cancer"},{"subject":"Biological Sciences"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Chemistry"},{"subject":"Molecular Biology"},{"subject":"Genetics"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Cell Biology"},{"subject":"Biophysics"}],"contributors":[],"dates":[{"date":"2015-12-05","dateType":"Created"},{"date":"2019-08-19","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"MicroRNAs (miRNAs) play an important role in tumorigenesis, but their role in tumor-induced immune suppression is largely unknown. STAT3 signaling, a key pathway mediating immune suppression in the tumor microenvironment, is responsible for the transcription of several important miRNAs. In this study, we observed that miR-146a, a known important regulator of immune responses, was downregulated by blocking activated STAT3 in hepatocellular carcinoma (HCC) cells. Furthermore, miR-146a inhibition in HCC cells not only altered the STAT3 activation–associated cytokine profile but also reversed HCC-induced NK cell dysfunction \u003ci\u003ein vitro\u003c/i\u003e and improved the anti-tumor effect of lymphocytes in vivo. Importantly, ChIP and luciferase reporter assays confirmed that STAT3 directly bound to the miR-146a promoter and induced miR-146a expression. These findings indicated that miR-146a expression was regulated by aberrantly activated STAT3 in HCC cells and exerted negative effects on anti-tumor immune response, which resulted in the upregulation of cytokines such as TGF-β, IL-17, VEGF and downregulation of type I IFN to create an immunosuppressive microenvironment. This further insight into understanding the mechanism responsible for tumor-induced immune suppression highlights the potential application of miR-146a as a novel immunotherapeutic target for HCC.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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","url":"https://tandf.figshare.com/collections/miR_146a_is_dir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