A Novel 5'tRNA-derived Fragment TRF-Tyr Inhibits Tumor Progression by Targeting HnRNPD in Gastric Cancer

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Specialties Biochemistry
Cell Biology

Date 2025 Feb 14

PMID 39953522

Authors

Huaiping Cui

Zhaodong Liu

Lipan Peng

Lijun Liu

Xiaozhou Xie

Yudi Zhang

Zi Gao

Chi Zhang

Xinshuai Yu

Yonghao Hu

Jin Liu

Liang Shang

Leping Li

Affiliations

Soon will be listed here.

Abstract

Background: Transfer RNA-derived small RNAs (tsRNAs), including tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs), constitute a novel class of small noncoding RNAs (sncRNAs). tsRNAs have been linked to tumorigenesis and the progression of carcinogenesis; however, the precise molecular mechanism through which tRFs act in gastric cancer (GC) remains unknown.

Methods: tRF-Tyr is a potential GC tumor suppressor that was identified through high-throughput sequencing technology. The expression and subcellular localization of tRF-Tyr in GC were detected by via qRT‒PCR and FISH. RNA pull-down, mass spectrometry, RNA immunoprecipitation (RIP), dual-luciferase reporter and rescue assays were performed to explore the regulatory mechanisms through which tRF-Tyr acts in GC.

Results: tRF-Tyr was significantly downregulated and the downregulation of its mainly concentrated in the nuclei of GC cells. Functionally, tRF-Tyr inhibited the proliferation, invasiveness and migration of GC cells and promoted GC cells apoptosis in vitro; meanwhile, tRF-Tyr inhibited tumor growth in vivo. Mechanistically, tRF-Tyr bound directly to the hnRNPD protein and competitively inhibited the binding of hnRNPD to the c-Myc 3'UTR, thereby, regulating the c-Myc/Bcl2/Bax pathway and ultimately inhibiting the progression of GC.

Conclusions: This study focused on a novel GC suppressor, tRF-Tyr, and revealed a previously undiscovered mechanism that tRF-Tyr inhibits tumor progression by targeting hnRNPD. These findings provide new insight into the involvement of tRFs in GC and suggest a novel target for GC treatment.

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