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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
miRNA profiling in metastatic renal cell carcinoma reveals a tumour-suppressor effect for miR-215
N M A White1, H W Z Khella, J Grigull
1Department of Laboratory Medicine and Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada.
Background:
Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Metastatic RCC is difficult to treat. The 5-year survival rate for metastatic RCC is ≤10%. Recently, microRNAs (miRNAs) have been shown to have a role in cancer metastasis and potential as prognostic biomarkers in cancer.
Method:
We performed a miRNA microarray to identify a miRNA signature characteristic of metastatic compared with primary RCCs. We validated our results by quantitative real-time PCR. We performed experimental and bioinformatic analyses to explore the involvement of miR-215 in RCC progression and metastasis.
Results:
We identified 65 miRNAs that were significantly altered in metastatic compared with primary RCCs. We validated our results by examining the expression of miR-10b, miR-126, miR-196a, miR-204 and miR-215, in two independent cohorts of patients. We showed that overexpression of miR-215 decreased cellular migration and invasion in an RCC cell line model. In addition, through gene expression profiling, we identified direct and indirect targets of miR-215 that can contribute to tumour metastasis.
Conclusion:
Our analysis showed that miRNAs are altered in metastatic RCCs and can contribute to kidney cancer metastasis through different biological processes. Dysregulated miRNAs represent potential prognostic biomarkers and may have therapeutic applications in kidney cancer.
Insights
MicroRNAs (miRNAs) are altered in metastatic renal cell carcinoma (RCC), impacting kidney cancer progression. These dysregulated miRNAs show potential as prognostic biomarkers and therapeutic targets for metastatic RCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Renal cell carcinoma (RCC) is the most common adult kidney cancer.
- Metastatic RCC has a poor prognosis with a 5-year survival rate of ≤10%.
- MicroRNAs (miRNAs) are implicated in cancer metastasis and serve as potential prognostic biomarkers.
Purpose of the Study:
- To identify miRNA signatures distinguishing metastatic from primary RCC.
- To investigate the role of miR-215 in RCC progression and metastasis.
Main Methods:
- MicroRNA microarray analysis to identify differentially expressed miRNAs.
- Quantitative real-time PCR for validation in independent patient cohorts.
- Experimental and bioinformatic analyses to explore miR-215 function and targets.
Main Results:
- Identified 65 significantly altered miRNAs in metastatic RCC.
- Validated altered expression of miR-10b, miR-126, miR-196a, miR-204, and miR-215.
- Overexpression of miR-215 reduced RCC cell migration and invasion; identified miR-215 targets involved in metastasis.
Conclusions:
- miRNAs are dysregulated in metastatic RCC and contribute to kidney cancer metastasis.
- Altered miRNAs are potential prognostic biomarkers for kidney cancer.
- Dysregulated miRNAs may offer therapeutic strategies for metastatic RCC.
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