标题:miR-146a is directly regulated by STAT3 in human hepatocellular carcinoma cells and involved in anti-tumor immune suppression
作者:Sun, Xiaoxia;Zhang, Jian;Hou, Zhaohua;Han, Qiuju;Zhang, Cai;Tian, Zhigang
作者机构:[Sun, X] Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China;[ Zhang, J] 更多
通讯作者:Zhang, J
通讯作者地址:[Zhang, J]Shandong Univ, Sch Pharmaceut Sci, Inst Immunopharmacol & Immunotherapy, Jinan 250100, Shandong, Peoples R China.
来源:Cell cycle
出版年:2015
卷:14
期:2
页码:243-252
DOI:10.4161/15384101.2014.977112
关键词:anti-tumor immune suppression;HCC;miRNA;miR-146a;STAT3
摘要: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 in vitro 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-, 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.
收录类别:SCOPUS;SCIE
WOS核心被引频次:25
Scopus被引频次:25
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84926675081&doi=10.4161%2f15384101.2014.977112&partnerID=40&md5=08a97c4857f94dce802420efb192b7b3
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