miR-146a negatively regulates NK cell functions via STAT1 signaling

摘要

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)-γand 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-αand 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.