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Published on: February 8, 2020
5'-tRNA Halves are Dysregulated in Clear Cell Renal Cell Carcinoma
Chenming Zhao1, Yuri Tolkach1, Doris Schmidt1
1Departments of Urology and Pathology (YT, GK), University Hospital Bonn, Bonn, Germany.
Purpose:
In various malignancies RNA fragments are dysregulated. Our study was designed to determine the expression of 4, 5'-tRNA halves in the tissue and serum of patients with clear cell renal cell carcinoma.
Materials And Methods:
Tissue and serum samples of patients with clear cell renal cell carcinoma and nonmalignant disease were collected prospectively in our biobank. We isolated total RNA from 95 clear cell renal cell carcinomas and 50 normal renal tissues as well as serum RNA from 27 patients with clear cell renal cell carcinoma and 13 with nonmalignant urological disease. To specifically determine the expression of 5'-tRNA halves we dephosphorylated and ligated an adaptor nucleotide to the 3' end of the tRNA halves. The expression levels of 4, 5'-tRNA halves (5'-tRNA-Arg-CCT, 5'-tRNA-Glu-CTC, 5'-tRNA-Leu-CAG and 5'-tRNA-Lys-TTT) were then measured by TaqMan® based quantitative reverse transcription-polymerase chain reaction.
Results:
All studied 5'-tRNA halves were down-regulated in clear cell renal cell carcinoma tissues, indicating a potential role as a tumor suppressor. Furthermore, we noted decreased expression of 5'-tRNA halves in patients with adverse clinicopathological parameters. All 5'-tRNA halves were expressed at lower levels in nonorgan confined clear cell renal cell carcinoma. The 5'-tRNA-Lys-TTT halves inversely correlated with ISUP (International Society of Urological Pathology) grade. In patients with clear cell renal cell carcinoma 5'-tRNA-Arg-CCT, 5'-tRNA-Glu-CTC and 5'-tRNA-Lys-TTT halves circulated at lower levels than in control subjects, indicating relevance as noninvasive biomarkers.
Conclusions:
In patients with clear cell renal cell carcinoma 5'-tRNA halves have potential as diagnostic and prognostic biomarkers. The 5'-tRNA halves may act in a tumor suppressive manner, which requires further research to confirm.
Insights
Four types of 5'-tRNA halves were found to be downregulated in clear cell renal cell carcinoma tissues and serum. These fragments may serve as diagnostic and prognostic biomarkers for kidney cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- RNA fragments, specifically tRNA halves, are dysregulated in various malignancies.
- Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer.
Purpose of the Study:
- To investigate the expression levels of four specific 5 RNA halves in ccRCC tissues and serum.
- To evaluate the potential of these 5 RNA halves as diagnostic and prognostic biomarkers for ccRCC.
Main Methods:
- Prospective collection of tissue and serum samples from ccRCC patients and non-malignant controls.
- Isolation of total RNA and specific quantification of 5 RNA-Arg-CCT, 5 RNA-Glu-CTC, 5 RNA-Leu-CAG, and 5 RNA-Lys-TTT using TaqMan®-based qRT-PCR.
- Analysis of expression levels in relation to clinicopathological parameters and disease status.
Main Results:
- All four studied 5 RNA halves were significantly downregulated in ccRCC tissues compared to normal renal tissues.
- Decreased expression of 5 RNA halves correlated with adverse clinicopathological parameters, including nonorgan-confined disease and higher ISUP grade (for 5 RNA-Lys-TTT).
- Lower serum levels of 5 RNA-Arg-CCT, 5 RNA-Glu-CTC, and 5 RNA-Lys-TTT were observed in ccRCC patients compared to controls, suggesting potential as noninvasive biomarkers.
Conclusions:
- The studied 5 RNA halves demonstrate potential as diagnostic and prognostic biomarkers for ccRCC.
- The downregulation of 5 RNA halves in ccRCC suggests a possible tumor-suppressive role that warrants further investigation.
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