tRF-3005a regulates exon skipping of SPAG4 by interacting with RALY to drive gastric cancer progression

作者：Huaiping Cui, Yancong Yuan, Yizhe Yin, Ruihong Gao, Zhaodong Liu, Lipan Peng, Jinshen Wang, Zhu Wang, Tingting Song, Jinglei Liu · 发表于：Cell Death Discovery · 年份：2026 · DOI：10.1038/s41420-026-03049-3 · 被引用次数：1 · 研究领域：RNA modifications and cancer、RNA and protein synthesis mechanisms、RNA Research and Splicing

Transfer RNA-derived fragments (tRFs) are emerging regulators in cancer, yet their role in the development and progression of gastric cancer (GC) remains unclear. Through RNA sequencing technology, this study identified a tRNA-derived fragment, tRF-3005a, that is significantly upregulated in GC tissues and cell lines and is associated with poor prognosis. Functionally, it promotes the proliferation, migration, and invasion of GC cells. Mechanistically, tRF-3005a bound to RALY, enhancing its interaction with SPAG4 mRNA, suppressing exon 8 skipping and leading to an increased generation of oncogenic SPAG4-L isoforms, thereby activating GRB14/PI3K/AKT signaling and ultimately promoting GC progression. This study reveals a novel mechanism wherein tRF-3005a promotes gastric cancer development by regulating RALY-mediated alternative splicing of SPAG4 to activate the GRB14/PI3K/AKT pathway, suggesting it may serve as a prognostic biomarker and therapeutic target.