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

## TL;DR

A tRNA fragment called tRF-3005a promotes gastric cancer by altering gene splicing and activating a cancer-driving pathway.

## Contribution

The study identifies a new tRF, tRF-3005a, that drives gastric cancer by regulating RALY-mediated splicing of SPAG4.

## Key findings

- tRF-3005a is upregulated in gastric cancer tissues and linked to poor prognosis.
- tRF-3005a promotes cancer cell growth and invasion by suppressing exon 8 skipping in SPAG4.
- tRF-3005a activates the GRB14/PI3K/AKT signaling pathway through RALY interaction.

## Abstract

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.