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...

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Main Authors: Chenwei Pan, Luxia Xiang, Zhenzhen Pan, Xiaodong Wang, Jie Li, Lu Zhuge, Peipei Fang, Qipeng Xie, Xuezhen Hu
Format: Article
Language:English
Published: BMC 2018-04-01
Series:Cancer Cell International
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12935-018-0542-y
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author Chenwei Pan
Luxia Xiang
Zhenzhen Pan
Xiaodong Wang
Jie Li
Lu Zhuge
Peipei Fang
Qipeng Xie
Xuezhen Hu
author_facet Chenwei Pan
Luxia Xiang
Zhenzhen Pan
Xiaodong Wang
Jie Li
Lu Zhuge
Peipei Fang
Qipeng Xie
Xuezhen Hu
author_sort Chenwei Pan
collection DOAJ
description 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.
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spelling doaj.art-27e22f891cdf42819bd3c055f0d9bdbf2022-12-22T01:57:14ZengBMCCancer Cell International1475-28672018-04-0118111110.1186/s12935-018-0542-yMiR-544 promotes immune escape through downregulation of NCR1/NKp46 via targeting RUNX3 in liver cancerChenwei Pan0Luxia Xiang1Zhenzhen Pan2Xiaodong Wang3Jie Li4Lu Zhuge5Peipei Fang6Qipeng Xie7Xuezhen Hu8Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityAbstract 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.http://link.springer.com/article/10.1186/s12935-018-0542-ymiR-544RUNX3NCR1NK cellsImmune escape
spellingShingle Chenwei Pan
Luxia Xiang
Zhenzhen Pan
Xiaodong Wang
Jie Li
Lu Zhuge
Peipei Fang
Qipeng Xie
Xuezhen Hu
MiR-544 promotes immune escape through downregulation of NCR1/NKp46 via targeting RUNX3 in liver cancer
Cancer Cell International
miR-544
RUNX3
NCR1
NK cells
Immune escape
title MiR-544 promotes immune escape through downregulation of NCR1/NKp46 via targeting RUNX3 in liver cancer
title_full MiR-544 promotes immune escape through downregulation of NCR1/NKp46 via targeting RUNX3 in liver cancer
title_fullStr MiR-544 promotes immune escape through downregulation of NCR1/NKp46 via targeting RUNX3 in liver cancer
title_full_unstemmed MiR-544 promotes immune escape through downregulation of NCR1/NKp46 via targeting RUNX3 in liver cancer
title_short MiR-544 promotes immune escape through downregulation of NCR1/NKp46 via targeting RUNX3 in liver cancer
title_sort mir 544 promotes immune escape through downregulation of ncr1 nkp46 via targeting runx3 in liver cancer
topic miR-544
RUNX3
NCR1
NK cells
Immune escape
url http://link.springer.com/article/10.1186/s12935-018-0542-y
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