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Comprehensively Identifying the Key tRNA-Derived Fragments and Investigating Their Function in Gastric Cancer
Xiaolin Dong1,2, Xirui Fan3, Xiaoxue He3
1Department of Neurology, The Affiliated Yan'An Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China.
Purpose:
Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide. tRNA-derived fragments (tRFs) have been identified as potential biomarkers and cancer therapeutic targets. However, the influence of tRFs on GC remains unknown. The key tRFs were researched in vitro function and mechanism.
Patients And Methods:
Here, differentially expressed tRFs between GC and paracancerous tissues were identified by small RNA sequencing, and the role of key tRF was evaluated in vitro.
Results:
Eight tRFs were significantly differentially expressed between GC tissues and adjacent tissues: five were significantly upregulated and three were downregulated in GC tissues. The results of target gene prediction and functional enrichment analysis showed that tRFs with different expressions were mainly involved in cell adhesion and connection, cell migration, wingless-type (Wnt), mitogen-activated protein kinase (MAPK), and cancer signaling pathways. Quantitative real-time polymerase chain reaction (qRT-PCR) indicated that the expression of tRF-24-V29K9UV3IU and its target genes (CCND2, FZD3, and VANGL1) in GC tissues and cells was decreased compared with those in the control group. Importantly, overexpression of tRF-24-V29K9UV3IU inhibited cell proliferation, migration and invasion, while promoted cell apoptosis of GC cells.
Conclusion:
This study suggests that tRF-24-V29K9UV3IU may hinder GC tumor progression by inhibiting cell proliferation, migration, invasion, while promoting cell apoptosis by regulating the Wnt signaling pathways.
Insights
This study identified key tRNA-derived fragments (tRFs) in gastric cancer (GC). The tRF-24-V29K9UV3IU was found to inhibit GC progression by reducing cell proliferation and migration, while promoting apoptosis.
Area of Science:
- Molecular Biology
- Oncology
- Genomics
Background:
- Gastric cancer (GC) is a leading cause of cancer mortality globally.
- tRNA-derived fragments (tRFs) show potential as cancer biomarkers and therapeutic targets.
- The specific roles of tRFs in GC development are largely unknown.
Purpose of the Study:
- To identify differentially expressed tRFs in GC tissues.
- To investigate the in vitro function and molecular mechanisms of key tRFs in GC.
- To explore the potential of tRFs as therapeutic targets for gastric cancer.
Main Methods:
- Small RNA sequencing to identify differentially expressed tRFs between GC and adjacent tissues.
- In vitro experiments to evaluate the functional role of a specific tRF (tRF-24-V29K9UV3IU).
- Quantitative real-time polymerase chain reaction (qRT-PCR) to validate expression levels of tRFs and target genes.
Main Results:
- Eight tRFs were significantly differentially expressed in GC tissues; five upregulated and three downregulated.
- tRF-24-V29K9UV3IU and its target genes (CCND2, FZD3, VANGL1) showed decreased expression in GC.
- Overexpression of tRF-24-V29K9UV3IU inhibited GC cell proliferation, migration, and invasion, while promoting apoptosis.
Conclusions:
- tRF-24-V29K9UV3IU may act as a tumor suppressor in gastric cancer.
- This tRF hinders GC progression by regulating Wnt signaling pathways.
- tRF-24-V29K9UV3IU warrants further investigation as a potential therapeutic agent for GC.
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