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

Frontiers in Oncology

Tianwei Jiang¹  Qi Zhou²  Lujun Chen⁴  Yuan Li⁴  Xiao Zheng⁴  Yuanyuan Fu⁴  Changping Wu⁴  Juan Liu⁴  Liping Guan⁴  Jingfang Ju⁶ 

[1] Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China;Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China;Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, China;Institute of Cell Therapy, Soochow University, Changzhou, China;Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, China;Translational Research Laboratory, Department of Pathology, Stony Brook University, Stony Brook, NY, United States;

关键词: long non-coding RNA;    lncRNA GRIK1-AS1;    miR-375;    IFIT2;    gastric cancer;   

DOI  :  10.3389/fonc.2021.754834

来源: DOAJ

【 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.

【 授权许可】

Unknown