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Identification and potential mechanism of a novel gastric cancer suppressor tRF-24-6VR8K09LE9
Yelan Tang1,2, Kan Ni3, Kangfeng Jin1,2
1Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226006, China.
Abstract:
One of the most common gastrointestinal tumors is gastric cancer (GC), which has a high lethality and a poor prognosis. Recently, it was discovered that mature tRNAs, which are expressed differently in a variety of malignancies, give rise to a novel class of tRNA-derived small RNAs (tsRNAs). In this study, we investigated the role of short RNAs produced from tRNA in GC and possible therapeutic uses. edgeR was used to screen the differentially expressed tsRNAs from the TCGA database and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was used to verify the levels of tsRNAs in GC samples. tRF-24-6VR8K09LE9 downregulated in GC was confirmed by detecting serum samples from 114 patients with gastric cancer, 40 patients with gastritis, and 100 healthy controls. The chi-square test displayed that tRF-24-6VR8K09LE9 was highly related to differentiation grade (P = 0.029), T-stage (P = 0.036), lymph node status (P = 0.036), TNM staging (P < 0.0001), and neurological/vascular invasion (P = 0.033). The receiver operating characteristic (ROC) curve indicated that tRF-24-6VR8K09LE9 is more effective than the current diagnostic markers for GC. Furthermore, mechanistic studies verified that tRF-24-6VR8K09LE9 affected the malignant progression of GC through the PI3K/AKT signaling pathway. In conclusion, tRF-24-6VR8K09LE9 can be served as a molecular marker for early GC auxiliary diagnosis. Over-expression of tRF-24-6VR8K09LE9 inhibits the malignant progression of GC, which may provide a new strategy for the adjuvant treatment of GC.
Insights
This study identifies a novel biomarker, tRF-24-6VR8K09LE9, for early gastric cancer (GC) detection. Its downregulation in GC patients suggests potential as a diagnostic marker and therapeutic target for this lethal disease.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gastric cancer (GC) is a leading cause of cancer mortality with a poor prognosis.
- TRNA-derived small RNAs (tsRNAs) are emerging as critical regulators in various malignancies.
- Investigating tsRNAs in GC may reveal novel diagnostic markers and therapeutic strategies.
Purpose of the Study:
- To explore the role of tsRNAs in gastric cancer.
- To identify potential diagnostic biomarkers for early GC detection.
- To investigate the therapeutic implications of specific tsRNAs in GC progression.
Main Methods:
- Differential expression analysis of tsRNAs using TCGA database and edgeR.
- Validation of tsRNA levels in patient serum samples via qRT-PCR.
- Correlation analysis (chi-square test) and diagnostic efficacy assessment (ROC curve) of identified tsRNAs.
- Mechanistic studies involving the PI3K/AKT signaling pathway.
Main Results:
- A specific tsRNA, tRF-24-6VR8K09LE9, was found to be significantly downregulated in GC patient serum.
- tRF-24-6VR8K09LE9 levels correlated strongly with GC differentiation, stage, lymph node status, and TNM staging.
- The receiver operating characteristic (ROC) curve analysis demonstrated superior diagnostic accuracy for tRF-24-6VR8K09LE9 compared to existing markers.
- Mechanistic investigations revealed that tRF-24-6VR8K09LE9 influences GC progression via the PI3K/AKT pathway.
Conclusions:
- tRF-24-6VR8K09LE9 serves as a promising molecular marker for the auxiliary diagnosis of early gastric cancer.
- Overexpression of tRF-24-6VR8K09LE9 demonstrates potential in inhibiting GC malignant progression.
- This tsRNA offers a novel strategy for the adjuvant treatment of gastric cancer.
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