title: miR-146a negatively regulates NK cell functions via STAT1 signaling.
abstract: 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.
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Xu
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Han
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Hou
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology*; D008113:Liver Neoplasms / Q000276:immunology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D016207:Cytokines; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human