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Expression profile of tRNA-derived fragments in pancreatic cancer
Lei Jin1,2, Chunfu Zhu1, Xihu Qin1
1Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213003, P.R. China.
Abstract:
Pancreatic cancer is a deadly disease, the deadliest of all the solid tumors; the 5-year survival rate of patients with this disease is ~8%. Previously, high-throughput sequencing has led to the discovery of novel small non-coding RNAs, also known as transfer RNA-derived fragments (tRFs). Studies have suggested that tRFs may be novel biomarkers for certain diseases. However, the expression of tRFs in pancreatic cancer has yet to be characterized. In the present study, the expression levels of tRFs observed in clinical pancreatic cancer samples were analyzed, quantitative PCR (qPCR) was performed to validate the tRFs expression levels and bioinformatics predictions were analyzed. The results revealed that the pancreatic cancer samples screened out a total of 48 tRFs and transfer RNA halves (tiRNAs). There were four tRFs and tiRNAs selected for qPCR validation; the findings were consistent with the sequencing results. Bioinformatic predictions revealed that AS-tDR-000064 was predicted to have 2,450 target genes; AS-tDR-000069 was predicted 445 target genes; AS-tDR-000102 was predicted 746 target genes; and AS-tDR-001391 was predicted 216 target genes. Gene Ontology (GO) analyses demonstrated that the target genes of AS-tDR-000064 were mostly enriched in 'the regulation of cellular processes' (Biological Process), 'the synapses' (Cellular Component) and 'enzyme binding' (Molecular Function). The target genes of AS-tDR-000069 were mostly enriched in 'signaling' (Biological Process), 'the plasma membrane' (Cellular Component) and 'phosphatidylinositol 3-kinase (PI3K) binding'(Molecular Function), the target genes of AS-tDR-000102 were mostly enriched in 'axon development' (Biological Process), 'the synapse' (Cellular Component) and 'sequence-specific DNA binding' (Molecular Function) and the target genes of AS-tDR-001391 were mostly enriched in 'the neuromuscular processes' (Biological Process), the neurons' (Cellular Component) and 'PDZ domain binding' (Molecular Function). The Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the target genes of AS-tDR-000064 were mostly enriched in 'the Ras signaling pathway', the target genes of AS-tDR-000069 were mostly enriched in 'the cancer pathways', the target genes of AS-tDR-000102 were mostly enriched in 'axon guidance' and the target genes of AS-tDR-001391 were mostly enriched in 'the PI3K/protein kinase-B signaling pathway'.
Insights
Transfer RNA-derived fragments (tRFs) show altered expression in pancreatic cancer, potentially serving as novel biomarkers. This study identified 48 tRFs and transfer RNA halves (tiRNAs) in tumors, with four validated by qPCR.
Area of Science:
- Molecular Biology
- Genomics
- Oncology
Background:
- Pancreatic cancer has a low 5-year survival rate (~8%).
- Small non-coding RNAs, including transfer RNA-derived fragments (tRFs), are increasingly recognized for their roles in disease.
- The expression profile of tRFs in pancreatic cancer remains largely uncharacterized.
Purpose of the Study:
- To characterize the expression levels of tRFs in clinical pancreatic cancer samples.
- To validate identified tRFs using quantitative PCR (qPCR).
- To predict and analyze the target genes and associated biological pathways of dysregulated tRFs using bioinformatics.
Main Methods:
- High-throughput sequencing to identify tRFs and transfer RNA halves (tiRNAs) in pancreatic cancer samples.
- Quantitative PCR (qPCR) for validation of selected tRFs/tiRNAs.
- Bioinformatic analyses including target gene prediction, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.
Main Results:
- A total of 48 tRFs and tiRNAs were identified in pancreatic cancer samples.
- qPCR validation confirmed the sequencing results for four selected tRFs/tiRNAs.
- Bioinformatic predictions identified numerous target genes for specific tRFs, enriched in pathways such as Ras signaling, cancer pathways, and PI3K/Akt signaling.
Conclusions:
- This study provides the first comprehensive characterization of tRF and tiRNA expression in pancreatic cancer.
- Specific tRFs and tiRNAs are dysregulated in pancreatic cancer and may serve as potential diagnostic or prognostic biomarkers.
- The identified target genes and pathways offer insights into the functional roles of tRFs in pancreatic cancer development and progression.
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