miR-146a negatively regulates NK cell functions via STAT1 signaling
miR-146a negatively regulates NK cell functions via STAT1 signaling
复制标题
miR-146a 通过 STAT1 信号传导负向调节 NK 细胞功能
DOI：
10.1038/cmi.2015.113
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发表时间：
2017-08-01
影响因子：
24.1
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Xu, Dongqing;Han, Qiuju;Zhang, Jian
It is known that natural killer (NK) cell function is downregulated in chronic hepatitis B (CHB)-infected patients and in hepatic carcinoma (HCC) patients, but the mechanisms underlying this functional downregulation are largely unclear. In this study, microRNA (miR)-146a expression increased in NK cells from CHB and HCC patients compared with NK cells from healthy donors, and miR-146a levels were negatively correlated to NK cell functions. Overexpression of miR-146a reduced NK cell-mediated cytotoxicity and the production of interferon (IFN)-γ and tumor necrosis factor-α, which were reversed upon inhibition of miR-146a. In NK cells, miR-146a expression was induced by interleukin (IL)-10 and transforming growth factor-β, but reduced after treatment with interleukin-12, IFN-α and IFN-β. We further revealed that miR-146a regulated NK cell functions by targeting STAT1. Taken together, upregulated miR-146a expression, at least partially, attributes to NK cell dysfunction in CHB and HCC patients. Therefore, miR-146a may become a therapeutic target with great potential to ameliorate NK cell functions in liver disease.
