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Open AccessArticle

Cancer Cells’ Metabolism Dynamics in Renal Cell Carcinoma Patients’ Outcome: Influence of GLUT-1-Related hsa-miR-144 and hsa-miR-186

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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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ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, 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—NRNorte), Estrada da Circunvalação 6657, 4200-177 Porto, Portugal
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Clinical Chemistry Department, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal
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Life and Health Sciences Research Institute (ICVS), School of Medicine, Campos de Gualtar, University of Minho, 4710-057 Braga, Portugal
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ICVS/3B’s—PT Government Associate Laboratory, 4710-057 Braga, Portugal
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ICVS/3B’s—PT Government Associate Laboratory, 4835-258 Guimarães, Portugal
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Biomedical Reasearch Center (CEBIMED, Faculty of Health Sciences, Fernando Pessoa University (UFP), Praça 9 de Abril 349, 4249-004 Porto, Portugal
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Faculty of Medicine (FMUP), University of Porto, 4200-319 Porto, Portugal
*
Author to whom correspondence should be addressed.
Academic Editors: Bi-Dar Wang and Luciane R Cavalli
Cancers 2021, 13(7), 1733; https://doi.org/10.3390/cancers13071733
Received: 23 March 2021 / Accepted: 1 April 2021 / Published: 6 April 2021
(This article belongs to the Special Issue The Roles of microRNAs in Cancer Aggressiveness and Drug Resistance)
Renal cell carcinoma (RCC) is a metabolic associated cancer and the most common and lethal neoplasia in the adult kidney. This study aimed to understand the potential role of hsa-miR-144-5p and hsa-miR-186-3p (which target Glucose Transporter 1—GLUT-1) in clear cell RCC (ccRCC) glycolysis status, as well as their potential as biomarkers. A decrease of intracellular levels of these miRNAs and increase of their excretion was associated with an increase of GLUT-1’s levels and glycolysis’ markers. RCC patients presented higher plasmatic levels of hsa-miR-186-3p than healthy individuals and hsa-miR144-5p’s higher levels were associated with early clinical stages of RCC. Additionally, patients with low plasmatic levels of hsa-miR-144-5p and high plasmatic levels of hsa-miR-186-3p (high-risk group) showed a worse overall survival. Overall, these results indicate that circulating hsa-miR-144-5p and hsa-miR-186-3p may be potential biomarkers of ccRCC prognosis.
The cancer cells’ metabolism is altered due to deregulation of key proteins, including glucose transporter 1 (GLUT-1), whose mRNA levels are influenced by microRNAs (miRNAs). Renal cell carcinoma (RCC) is the most common and lethal neoplasia in the adult kidney, mostly due to the lack of accurate diagnosis and follow-up biomarkers. Being a metabolic associated cancer, this study aimed to understand the hsa-miR-144-5p and hsa-miR-186-3p’s potential as biomarkers of clear cell RCC (ccRCC), establishing their role in its glycolysis status. Using three ccRCC lines, the intra- and extracellular levels of both miRNAs, GLUT-1’s mRNA expression and protein levels were assessed. Glucose consumption and lactate production were evaluated as glycolysis markers. A decrease of intracellular levels of these miRNAs and increase of their excretion was observed, associated with an increase of GLUT-1’s levels and glycolysis’ markers. Through a liquid biopsy approach, we found that RCC patients present higher plasmatic levels of hsa-miR-186-3p than healthy individuals. The Hsa-miR144-5p’s higher levels were associated with early clinical stages. When patients were stratified according to miRNAs plasmatic levels, low plasmatic levels of hsa-miR-144-5p and high plasmatic levels of hsa-miR-186-3p (high-risk group) showed the worst overall survival. Thus, circulating levels of these miRNAs may be potential biomarkers of ccRCC prognosis. View Full-Text
Keywords: renal cell carcinoma; microRNAs; biomarkers; Warburg effect; glucose transporter 1 renal cell carcinoma; microRNAs; biomarkers; Warburg effect; glucose transporter 1
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MDPI and ACS Style

Morais, M.; Dias, F.; Nogueira, I.; Leão, A.; Gonçalves, N.; Araújo, L.; Granja, S.; Baltazar, F.; Teixeira, A.L; Medeiros, R. Cancer Cells’ Metabolism Dynamics in Renal Cell Carcinoma Patients’ Outcome: Influence of GLUT-1-Related hsa-miR-144 and hsa-miR-186. Cancers 2021, 13, 1733. https://doi.org/10.3390/cancers13071733

AMA Style

Morais M, Dias F, Nogueira I, Leão A, Gonçalves N, Araújo L, Granja S, Baltazar F, Teixeira AL, Medeiros R. Cancer Cells’ Metabolism Dynamics in Renal Cell Carcinoma Patients’ Outcome: Influence of GLUT-1-Related hsa-miR-144 and hsa-miR-186. Cancers. 2021; 13(7):1733. https://doi.org/10.3390/cancers13071733

Chicago/Turabian Style

Morais, Mariana; Dias, Francisca; Nogueira, Inês; Leão, Anabela; Gonçalves, Nuno; Araújo, Luís; Granja, Sara; Baltazar, Fátima; Teixeira, Ana L; Medeiros, Rui. 2021. "Cancer Cells’ Metabolism Dynamics in Renal Cell Carcinoma Patients’ Outcome: Influence of GLUT-1-Related hsa-miR-144 and hsa-miR-186" Cancers 13, no. 7: 1733. https://doi.org/10.3390/cancers13071733

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