MiR-544 promotes immune escape through downregulation of NCR1/NKp46 via targeting RUNX3 in liver cancer

Autor: Chenwei Pan, Luxia Xiang, Zhenzhen Pan, Xiaodong Wang, Jie Li, Lu Zhuge, Peipei Fang, Qipeng Xie, Xuezhen Hu
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Cancer Cell International, Vol 18, Iss 1, Pp 1-11 (2018)
Druh dokumentu: article
ISSN: 1475-2867
DOI: 10.1186/s12935-018-0542-y
Popis: Abstract Objective To study the potential role of miR-544 in the immune escape mechanism of hepatoma cells. Methods Natural killer (NK) cells were collected from healthy volunteers and patients with liver cancer. Interleukin (IL)-2 activated-NK-92 cells were transfected with miR-544 inhibitor/mimic or NC/pre-NC in HepG2 co-culture system. NK-92 cells were treated with control, IL-2, IL-2 + pre-NC, IL-2 + miR-544 mimic, IL-2 + miR-544 mimic + pcDNA and IL-2 + miR-544 mimic + pcDNA-runt-related transcription factor 3 (RUNX3) groups. Mice models of liver cancer were well established. Expression of miR-544, natural cytotoxicity receptor 1 (NCR1) and RUNX3 were evaluated by quantitative real-time PCR and western blotting. Flow cytometry and ELISA were used to determine NK cell cytotoxicity and the levels of INF-γ, respectively. Results MiR-544 was upregulated while NCR1 and RUNX3 was downregulated in NK cells of patients with liver cancer. The levels of IFN-γ and miR-544 expression were increased and decreased in IL-2 activated-NK cells, respectively. Inversely, miR-544 overexpression inhibited NK cell cytotoxicity by downregulating IFN-γ. However, miR-544 directly targeted RUNX3 and negatively regulated NCR1. Furthermore, miR-544 promoted immune escape of hepatoma cells in vivo and in vitro. Conclusion miR-544 promoted the immune escape of liver cancer cells by downregulating NCR1 via targeting RUNX3.
Databáze: Directory of Open Access Journals
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