LncRNA GAS5 enhanced the killing effect of NK cell on liver cancer through regulating miR-544/RUNX3

Author:

Fang Peipei12,Xiang Luxia123,Chen Weilai4,Li Shaoxun123,Huang Shanshan1,Li Jie1,Zhuge Lu1,Jin Lingxiang1,Feng Wenke2,Chen Yiping2,Pan Chenwei12ORCID

Affiliation:

1. Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China

2. Pediatric Hepatitis and Liver disease Clinical Center, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China

3. The Second School of Medicine, Wenzhou Medical University, People’s Republic of China

4. Department of Neurology, Wenzhou People’s Hospital, People’s Republic of China

Abstract

This study aimed to explore the role of lncRNA GAS5 in the regulation of the killing effect of NK cells on liver cancer. Compared with a control group, lncRNA GAS5, RUNX3, and NCR1 were down-regulated in NK cells of patients with liver cancer, whereas miR-544 expression was up-regulated in NK cells of patients with liver cancer. Activated NK cells had higher IFN-γ level. Knockdown of GAS5 in activated NK cells decreased IFN-γ secretion, NK cell cytotoxicity, the percentage of CD107a+ NK cells, and the apoptosis rate of HepG2 and Huh7 cells. We also proved the interaction of GAS5 and miR-544, and the negative regulation role of GAS5 on miR-544. GAS5 overexpression in activated NK cells increased RUNX3 expression, IFN-γ secretion, the NK cell cytotoxicity, the percentage of CD107a+ NK cells, and the apoptosis rate of HepG2 cells, while miR-544 mimic abolished the promotion effect of GAS5 overexpression. Finally, in vivo experiments indicated an inhibition effect of GAS5 in tumor growth. LncRNA GAS5 overexpression enhances the killing effect of NK cell on liver cancer through regulating miR-544/RUNX3.

Funder

Zhejiang Provincial Natural Science Foundation of China

Publisher

SAGE Publications

Subject

Infectious Diseases,Cell Biology,Molecular Biology,Immunology,Microbiology

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