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

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.

journal_name

Cancer Cell Int

authors

Pan C,Xiang L,Pan Z,Wang X,Li J,Zhuge L,Fang P,Xie Q,Hu X

doi

10.1186/s12935-018-0542-y

subject

Has Abstract

pub_date

2018-04-03 00:00:00

pages

52

issn

1475-2867

pii

542

journal_volume

18

pub_type

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