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Updated: Jun 17, 2026

CRISPR Gene Editing Tool for MicroRNA Cluster Network Analysis
Published on: April 25, 2022
The miR-17-92 cluster is over expressed in and has an oncogenic effect on renal cell carcinoma
Tsz-Fung F Chow1, Marina Mankaruos, Andreas Scorilas
1Department of Laboratory Medicine and Keenan Research Centre, Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada.
Purpose:
miRNAs are small, nonprotein coding RNAs that are differentially expressed in many malignancies. We previously identified 80 miRNAs that are dysregulated in clear cell renal cell carcinoma. In this study we validated over expression of the miR-17-92 cluster in clear cell renal cell carcinoma and tested the effect of 2 members of this cluster (miR-17-5p and miR-20a) on tumor proliferation. We also elucidated the role of miRNA in clear cell renal cell carcinoma pathogenesis with bioinformatics.
Materials And Methods:
miRNA expression was validated by quantitative reverse transcriptase-polymerase chain reaction. The cell proliferation effect of miR-17-5p and miR-20a was tested in a renal adenocarcinoma cell line model. Multiple in silico analyses were done of dysregulated miRNAs.
Results:
We validated miR-71-92 cluster over expression in clear cell renal cell carcinoma by quantitative reverse transcriptase-polymerase chain reaction. Transfection of miR-20a inhibitor significantly decreased cell proliferation in a dose dependent manner. Transfection of miR-17-5p, which is not endogenously expressed in the ACHN cell line, led to increased cell proliferation compared to control values. This effect was suppressed by miR-17-5p inhibitor. Bioinformatics analysis identified 10 clusters of miRNAs dysregulated in clear cell renal cell carcinoma that followed the same expression patterns. We also identified matching patterns between reported chromosomal aberration in clear cell renal cell carcinoma and miRNA dysregulation for 37.5% of the miRNAs. Target prediction analysis was done using multiple algorithms. Many key molecules in clear cell renal cell carcinoma pathogenesis, including HIFs, mTOR, VEGF and VHL, were potential targets for dysregulated miRNAs.
Conclusions:
A significant number of dysregulated proteins in clear cell renal cell carcinoma are potential miRNA targets. Also, many clear cell renal cell carcinoma dysregulated miRNAs are phylogenetically conserved.
Insights
MicroRNAs (miRNAs) are dysregulated in clear cell renal cell carcinoma (ccRCC). miR-20a inhibits ccRCC proliferation, while miR-17-5p promotes it, suggesting therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are small, noncoding RNAs with critical roles in gene regulation.
- Aberrant miRNA expression is a hallmark of many cancers, including clear cell renal cell carcinoma (ccRCC).
- Previous work identified 80 dysregulated miRNAs in ccRCC.
Purpose of the Study:
- Validate the overexpression of the miR-17-92 cluster in ccRCC.
- Investigate the functional impact of miR-17-5p and miR-20a on ccRCC cell proliferation.
- Elucidate the role of miRNA dysregulation in ccRCC pathogenesis using bioinformatics.
Main Methods:
- Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) for miRNA expression validation.
- Renal adenocarcinoma cell line (ACHN) model to assess miRNA effects on proliferation.
- In silico analyses, including target prediction and pattern matching with genomic aberrations.
Main Results:
- miR-17-92 cluster overexpression was confirmed in ccRCC via qRT-PCR.
- miR-20a inhibition significantly reduced ccRCC cell proliferation in a dose-dependent manner.
- miR-17-5p transfection increased proliferation, an effect reversed by its inhibitor. Bioinformatics identified 10 miRNA clusters and linked miRNA dysregulation to chromosomal aberrations in 37.5% of cases. Key ccRCC molecules (HIFs, mTOR, VEGF, VHL) were predicted as miRNA targets.
Conclusions:
- Numerous dysregulated proteins in ccRCC are potential miRNA targets.
- Phylogenetically conserved miRNAs are frequently dysregulated in ccRCC.
- Specific miRNAs, like miR-20a and miR-17-5p, play opposing roles in ccRCC proliferation, offering potential therapeutic avenues.
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