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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Expanding the miRNA Transcriptome of Human Kidney and Renal Cell Carcinoma
Adam P Sage1, Brenda C Minatel1, Erin A Marshall1
1Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Abstract:
Despite advancements in therapeutic strategies, diagnostic and prognostic molecular markers of kidney cancer remain scarce, particularly in patients who do not harbour well-defined driver mutations. Recent evidence suggests that a large proportion of the human noncoding transcriptome has escaped detection in early genomic explorations. Here, we undertake a large-scale analysis of small RNA-sequencing data from both clear cell renal cell carcinoma (ccRCC) and nonmalignant samples to generate a robust set of miRNAs that remain unannotated in kidney tissues. We find that these novel kidney miRNAs are also expressed in renal cancer cell lines. Moreover, these sequences are differentially expressed between ccRCC and matched nonmalignant tissues, implicating their involvement in ccRCC biology and potential utility as tumour-specific markers of disease. Indeed, we find some of these miRNAs to be significantly associated with patient survival. Finally, target prediction and subsequent pathway analysis reveals that miRNAs previously unannotated in kidney tissues may target genes involved in ccRCC tumourigenesis and disease biology. Taken together, our results represent a new resource for the study of kidney cancer and underscore the need to characterize the unexplored areas of the transcriptome.
Insights
Researchers discovered novel kidney microRNAs (miRNAs) in clear cell renal cell carcinoma (ccRCC). These unannotated miRNAs show potential as diagnostic markers and are linked to patient survival in kidney cancer.
Area of Science:
- Genomics
- Molecular Biology
- Oncology
Background:
- Diagnostic and prognostic molecular markers for kidney cancer are limited, especially in patients without known driver mutations.
- A significant portion of the human noncoding transcriptome remains uncharacterized in genomic studies.
Purpose of the Study:
- To identify novel microRNAs (miRNAs) in kidney tissues using small RNA sequencing.
- To assess the expression and potential utility of these novel miRNAs as biomarkers in clear cell renal cell carcinoma (ccRCC).
Main Methods:
- Large-scale analysis of small RNA sequencing data from ccRCC and nonmalignant kidney tissues.
- Expression profiling of novel kidney miRNAs in ccRCC cell lines and patient tissues.
- Bioinformatic analysis for target prediction and pathway analysis.
Main Results:
- A set of previously unannotated kidney miRNAs were identified and found to be expressed in ccRCC cell lines.
- These novel miRNAs were differentially expressed between ccRCC and matched nonmalignant tissues.
- Several novel miRNAs were significantly associated with patient survival, suggesting prognostic value.
Conclusions:
- The identified novel kidney miRNAs are implicated in ccRCC biology and hold potential as tumor-specific diagnostic and prognostic markers.
- These findings highlight the importance of exploring the unannotated transcriptome for new insights into kidney cancer.
- This study provides a valuable resource for future research in kidney cancer diagnostics and therapeutics.
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