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

Qi Zhou; Yuan Li; Yuan Li; Yuan Li; Lujun Chen; Lujun Chen; Lujun Chen; Xiao Zheng; Xiao Zheng; Xiao Zheng; Tianwei Jiang; Juan Liu; Juan Liu; Juan Liu; Yuanyuan Fu; Yuanyuan Fu; Yuanyuan Fu; Liping Guan; Liping Guan; Liping Guan; Jingfang Ju; Changping Wu; Changping Wu; Changping Wu; Changping Wu

doi:10.3389/fonc.2021.754834

Frontiers in Oncology (Sep 2021)

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

Qi Zhou,
Yuan Li,
Yuan Li,
Yuan Li,
Lujun Chen,
Lujun Chen,
Lujun Chen,
Xiao Zheng,
Xiao Zheng,
Xiao Zheng,
Tianwei Jiang,
Juan Liu,
Juan Liu,
Juan Liu,
Yuanyuan Fu,
Yuanyuan Fu,
Yuanyuan Fu,
Liping Guan,
Liping Guan,
Liping Guan,
Jingfang Ju,
Changping Wu,
Changping Wu,
Changping Wu,
Changping Wu

Affiliations

Qi Zhou: Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China
Yuan Li: Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, China
Yuan Li: Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, China
Yuan Li: Institute of Cell Therapy, Soochow University, Changzhou, China
Lujun Chen: Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, China
Lujun Chen: Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, China
Lujun Chen: Institute of Cell Therapy, Soochow University, Changzhou, China
Xiao Zheng: Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, China
Xiao Zheng: Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, China
Xiao Zheng: Institute of Cell Therapy, Soochow University, Changzhou, China
Tianwei Jiang: Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
Juan Liu: Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, China
Juan Liu: Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, China
Juan Liu: Institute of Cell Therapy, Soochow University, Changzhou, China
Yuanyuan Fu: Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, China
Yuanyuan Fu: Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, China
Yuanyuan Fu: Institute of Cell Therapy, Soochow University, Changzhou, China
Liping Guan: Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, China
Liping Guan: Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, China
Liping Guan: Institute of Cell Therapy, Soochow University, Changzhou, China
Jingfang Ju: Translational Research Laboratory, Department of Pathology, Stony Brook University, Stony Brook, NY, United States
Changping Wu: Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China
Changping Wu: Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, China
Changping Wu: Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, China
Changping Wu: Institute of Cell Therapy, Soochow University, Changzhou, China

DOI: https://doi.org/10.3389/fonc.2021.754834
Journal volume & issue: Vol. 11

Abstract

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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.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

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