ELAVL1 facilitates gastric cancer progression and metastasis through TL1A mRNA stabilization

Abstract

ELAV-like RNA-binding protein 1 (ELAVL1) is a key RNA-binding protein involved in tumor progression and metastasis. This study identifies a previously unrecognized interaction between ELAVL1 and TL1A mRNA, elucidating its role in promoting gastric cancer (GC) progression through the activation of the PI3K/Akt signaling pathway. Overexpression of ELAVL1 significantly enhances the proliferation and migration of GC cells, whereas silencing ELAVL1 leads to a marked reduction in these processes. Additionally, stable knockout of ELAVL1 significantly inhibits the growth of xenograft tumors derived from GC cells in nude mice. Mechanistically, ELAVL1 directly binds to TL1A mRNA through its RNA recognition motifs (RRM1 and RRM3). The binding sites on TL1A mRNA have been confirmed in two regions: one located between nucleotides 1605 and 1868, and the other between 4324 and 4587. ELAVL1 stabilizes TL1A mRNA expression and promotes GC progression by activating the downstream PI3K/Akt signaling pathway.Our findings highlight a novel regulatory axis involving ELAVL1, TL1A mRNA, and PI3K/Akt, providing new insights into RNA-mediated oncogenic signaling and establishing ELAVL1 as a potential therapeutic target for GC. This discovery lays the groundwork for developing targeted therapies against ELAVL1.