Abstract LB302: circIPO7 dissociates caprin-1 from ribosomes and inhibits gastric cancer cell proliferation by suppressing EGFR and mTOR

Abstract

Abstract circIPO7 dissociates caprin-1 from ribosomes and inhibits gastric cancer cell proliferation by suppressing EGFR and mTORLiling Niu, Jing Liu, Hui Li*Purpose: Circular RNAs (circRNAs) are vital participant of various pathophysiological processes through unique mechanisms. We previously reported that circIPO7 (circBase ID: hsa_-circ_0005092) was positively associated with postoperative recurrence of gastric cancer (GC). In the present study, we aimed to explore the biological function of circIPO7 in GC development. Methods: CCK-8, clone formation, Edu proliferation assay and xenograft model were used to analyze the effects of circIPO7 and caprin-1 on the cell proliferation and tumor growth in vivo and in vitro. Mass spectrometry, RNA pull down, RIP and RNA-FISH experiments were used to identify the co-localization and interaction between caprin-1 and circIPO7. RIP sequencing was used to analyze the mRNAs binding with caprin-1. Rescue experiment was conducted to evaluate the translational regulation of circIPO7 on caprin-1 downstream effector molecule.Results: circIPO7 was downregulated in GC tissues and cells compared to paracarcinoma tissues and normal epithelial cells. circIPO7 overexpression significantly suppressed GC cell proliferation in vitro and in vivo. Mechanistically, circIPO7 directly binds with caprin-1, an RNA-binding protein involved in mRNA translation, sharing overlapping binding sites with G3BP1. Thus, the complex containing overexpressed circIPO7 blocked the caprin-1-G3BP1 interaction and dissociated caprin-1 and its target mRNAs (EGFR and mTOR) from ribosomes, resulting in their translational inhibition, followed by PI3K/AKT/mTOR pathway inactivation.Conclusion: We demonstrate that circIPO7 serves as an RBP sponge for caprin-1, inhibits the translation of downstream proliferation-related mRNAs, and ultimately suppresses malignant cell proliferation. Taken together, these results suggest that circIPO7 may be a potential therapeutic target for GC treatment. Citation Format: Liling Niu, Jing Liu, Hui Li. circIPO7 dissociates caprin-1 from ribosomes and inhibits gastric cancer cell proliferation by suppressing EGFR and mTOR [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB302.