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

Backgroud Long non-coding RNAs (lncRNAs) played important roles in various biological processes and human diseases, including cancer. Methods In this study, RNAi technology, RNA-FISH, RNA-pull down assay and cellular function studies were used to demonstrate a regulatory relationship between lncRNA GRIK1-AS1 and miR-375/IFIT2 axis in gastric cancer. Results 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 gene of miR-375, and established the important role of GRIK1-AS1/miR-375/IFIT2 axis in the progression of gastric cancer. Conclusions Our results revealed a novel mechanism of GRIK1-AS1 as sponge to miR-375that impact gastric cancer progression via modulating target mRNA IFIT2 translation, and as a result, open a new strategy to future GRIK1-AS1 based therapeutic development.