Long Non-Coding RNA GRIK1-AS1 Inhibits the Proliferation and Invasion of Gastric Cancer Cells by Regulating the miR-375/IFIT2 Axis

被引:5
作者
Zhou, Qi [1 ]
Li, Yuan [2 ,3 ,4 ]
Chen, Lujun [2 ,3 ,4 ]
Zheng, Xiao [2 ,3 ,4 ]
Jiang, Tianwei [5 ]
Liu, Juan [2 ,3 ,4 ]
Fu, Yuanyuan [2 ,3 ,4 ]
Guan, Liping [2 ,3 ,4 ]
Ju, Jingfang [6 ]
Wu, Changping [1 ,2 ,3 ,4 ]
机构
[1] Soochow Univ, Dept Oncol, Affiliated Hosp 3, Changzhou, Peoples R China
[2] Soochow Univ, Dept Tumor Biol Treatment, Affiliated Hosp 3, Changzhou, Peoples R China
[3] Jiangsu Engn Res Ctr Tumor Immunotherapy, Changzhou, Peoples R China
[4] Soochow Univ, Inst Cell Therapy, Changzhou, Peoples R China
[5] Soochow Univ, Dept Neurosurg, Affiliated Hosp 3, Changzhou, Peoples R China
[6] SUNY Stony Brook, Dept Pathol, Translat Res Lab, Stony Brook, NY 11794 USA
基金
中国国家自然科学基金;
关键词
long non-coding RNA; lncRNA GRIK1-AS1; miR-375; IFIT2; gastric cancer; EXPRESSION; STATISTICS; GENES; IFIT2;
D O I
10.3389/fonc.2021.754834
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Long non-coding RNAs (lncRNAs) play important roles in various biological processes and human diseases, including cancer. In this study, we demonstrated a regulatory relationship between lncRNA GRIK1-AS1 and miR-375/IFIT2 axis in gastric cancer. Our results show a decreased expression of GRIK1-AS1 in gastric cancer tissues compared to adjacent normal gastric tissues. Gastric cell lines also have reduced levels of GRIK1-AS1 compared to gastric epithelial cell line GES-1. Ectopic expression of GRIK1-AS1 in gastric cancer cell lines significantly inhibits cellular viability, migration, and invasion. RNA-pull down and the luciferase activity assays show that GRIK1-AS1 mainly interacts specifically with miR-375. We further demonstrate a negatively regulatory relationship between lncRNA GRIK1-AS1 and miR-375. We discovered that IFIT2 was one of the direct key downstream target genes of miR-375, and established the important role of the GRIK1-AS1/miR-375/IFIT2 axis in the progression of gastric cancer. Taken together, our results revealed a novel mechanism of GRIK1-AS1 as a sponge to miR-375 that impacts gastric cancer progression via modulating target mRNA IFIT2 translation, and as a result, opens a new strategy to future GRIK1-AS1 based therapeutic development.
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页数:9
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