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Extracellular Vesicles Enriched in hsa-miR-301a-3p and hsa-miR-1293 Dynamics in Clear Cell Renal Cell Carcinoma Patients: Potential Biomarkers of Metastatic Disease

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Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Research Center- LAB2, E Bdg 1st floor, Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal
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Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal
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Research Department of the Portuguese League Against Cancer Regional Nucleus of the North (LPCC-NRN), Estrada da Circunvalação 6657, 4200-177 Porto, Portugal
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Systems Oncology Group, Champalimaud Research, Champalimaud Centre for the Unknown, Av. Brasília, 1400-038 Lisbon, Portugal
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Graduate Program in Areas of Basic and Applied Biology (GABBA), University of Porto, 4200-135 Porto, Portugal
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Department of Medical Oncology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal
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Department of Urology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal
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Department of Pathology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal
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Cancer Biology and Epigenetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Research Center- LAB3, F Bdg 1st floor, Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal
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Department of Genetics, University Medical Center Groningen (UMCG), University of Groningen, Hanzeplein 1, 9713 GZ Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
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Faculty of Medicine, University of Porto (FMUP), Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
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Biomedical Research Center (CEBIMED), Faculty of Health Sciences of Fernando Pessoa University (UFP), Praça 9 de Abril 349, 4249-004 Porto, Portugal
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Author to whom correspondence should be addressed.
Cancers 2020, 12(6), 1450; https://doi.org/10.3390/cancers12061450
Received: 19 May 2020 / Accepted: 29 May 2020 / Published: 2 June 2020
(This article belongs to the Special Issue Noncoding RNAs in Renal Cell Carcinoma Landscape)
Clear cell renal cell carcinoma (ccRCC) is the most aggressive subtype of kidney cancer and up to 40% of patients submitted to surgery with a curative intent will relapse. Thus, the aim of this study was to analyze the applicability of an Extracellular vesicle (EV) derived miRNA profile as potential prognosis biomarkers in ccRCC patients. We analyzed a nine-miRNA profile in plasma EVs from 32 ccRCC patients with localized disease (before and after surgery) and in 37 patients with metastatic disease. We observed that the levels of EV-derived hsa-miR-25-3p, hsa-miR-126-5p, hsa-miR-200c-3p, and hsa-miR-301a-3p decreased after surgery, whereas hsa-miR-1293 EV-levels increased. Furthermore, metastatic patients presented higher levels of hsa-miR-301a-3p and lower levels of hsa-miR-1293 when compared to patients with localized disease after surgery. Functional enrichment analysis of the targets of the four miRNAs that decreased after surgery resulted in an enrichment of terms related to cell cycle, proliferation, and metabolism, suggesting that EV-miRNA enrichment in the presence of the tumor could represent an epigenetic mechanism to sustain tumor development. Taken together, these results suggest that EVs content varies depending on the presence or absence of the disease and that an increase of EV-derived hsa-miR-301a-3p, and decrease of EV-derived hsa-miR-1293, may be potential biomarkers of metastatic ccRCC. View Full-Text
Keywords: clear cell renal cell carcinoma; extracellular vesicles; microRNAs; biomarkers clear cell renal cell carcinoma; extracellular vesicles; microRNAs; biomarkers
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Dias, F.; Teixeira, A.L.; Nogueira, I.; Morais, M.; Maia, J.; Bodo, C.; Ferreira, M.; Silva, A.; Vilhena, M.; Lobo, J.; Sequeira, J.P.; Maurício, J.; Oliveira, J.; Kok, K.; Costa-Silva, B.; Medeiros, R. Extracellular Vesicles Enriched in hsa-miR-301a-3p and hsa-miR-1293 Dynamics in Clear Cell Renal Cell Carcinoma Patients: Potential Biomarkers of Metastatic Disease. Cancers 2020, 12, 1450.

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