Scholarlink

Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A novel 5’tRNA-derived fragment tRF-Tyr inhibits tumor progression by targeting hnRNPD in gastric cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月14日

查看全文
  • 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

摘要

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.