{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T01:50:19Z","timestamp":1772589019009,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The cancer cells\u2019 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\u2019s 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\u2019s 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\u2019s levels and glycolysis\u2019 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\u2019s 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.<\/jats:p>","DOI":"10.3390\/cancers13071733","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T10:34:12Z","timestamp":1617705252000},"page":"1733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Cancer Cells\u2019 Metabolism Dynamics in Renal Cell Carcinoma Patients\u2019 Outcome: Influence of GLUT-1-Related hsa-miR-144 and hsa-miR-186"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8406-8210","authenticated-orcid":false,"given":"Mariana","family":"Morais","sequence":"first","affiliation":[{"name":"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 Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"},{"name":"Research Department of the Portuguese League against Cancer Regional Nucleus of the North (LPCC\u2014NRNorte), Estrada da Circunvala\u00e7\u00e3o 6657, 4200-177 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4993-4467","authenticated-orcid":false,"given":"Francisca","family":"Dias","sequence":"additional","affiliation":[{"name":"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 Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"}]},{"given":"In\u00eas","family":"Nogueira","sequence":"additional","affiliation":[{"name":"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 Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"},{"name":"Research Department of the Portuguese League against Cancer Regional Nucleus of the North (LPCC\u2014NRNorte), Estrada da Circunvala\u00e7\u00e3o 6657, 4200-177 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2232-5693","authenticated-orcid":false,"given":"Anabela","family":"Le\u00e3o","sequence":"additional","affiliation":[{"name":"Clinical Chemistry Department, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Nuno","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Clinical Chemistry Department, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Lu\u00eds","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Clinical Chemistry Department, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Sara","family":"Granja","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, Campos de Gualtar, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4835-258 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1770-4544","authenticated-orcid":false,"given":"F\u00e1tima","family":"Baltazar","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, Campos de Gualtar, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4835-258 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7489-2211","authenticated-orcid":false,"given":"Ana L","family":"Teixeira","sequence":"additional","affiliation":[{"name":"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 Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8373","authenticated-orcid":false,"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"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 Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Research Department of the Portuguese League against Cancer Regional Nucleus of the North (LPCC\u2014NRNorte), Estrada da Circunvala\u00e7\u00e3o 6657, 4200-177 Porto, Portugal"},{"name":"Biomedical Reasearch Center (CEBIMED, Faculty of Health Sciences, Fernando Pessoa University (UFP), Pra\u00e7a 9 de Abril 349, 4249-004 Porto, Portugal"},{"name":"Faculty of Medicine (FMUP), University of Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1093\/annonc\/mdz056","article-title":"Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"30","author":"Escudier","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.eururo.2016.02.029","article-title":"The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs\u2014Part A: Renal, Penile, and Testicular Tumours","volume":"70","author":"Moch","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17009","DOI":"10.1038\/nrdp.2017.9","article-title":"Renal cell carcinoma","volume":"3","author":"Hsieh","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"611.e17","DOI":"10.1016\/j.cell.2018.02.020","article-title":"Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal","volume":"173","author":"Mitchell","year":"2018","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.eururo.2019.02.011","article-title":"European Association of Urology Guidelines on Renal Cell Carcinoma: The 2019 Update","volume":"75","author":"Ljungberg","year":"2019","journal-title":"Eur. Urol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3389\/fgene.2019.00169","article-title":"Blood Circulating miRNAs as Cancer Biomarkers for Diagnosis and Surgical Treatment Response","volume":"10","year":"2019","journal-title":"Front. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.biocel.2009.12.014","article-title":"MicroRNAs: Potential biomarkers for cancer diagnosis, prognosis and targets for therapy","volume":"42","author":"Cho","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103315","DOI":"10.18632\/oncotarget.21733","article-title":"Plasmatic miR-210, miR-221 and miR-1233 profile: Potential liquid biopsies candidates for renal cell carcinoma","volume":"8","author":"Dias","year":"2017","journal-title":"Oncotarget"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4057","DOI":"10.1007\/s13277-013-1531-3","article-title":"Higher circulating expression levels of miR-221 associated with poor overall survival in renal cell carcinoma patients","volume":"35","author":"Teixeira","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Teixeira, A.L., Dias, F., Ferreira, M., Gomes, M., Santos, J.I., Lobo, F., Mauricio, J., Machado, J.C., and Medeiros, R. (2014). Combined Influence of EGF+61G > A and TGFB+869T > C Functional Polymorphisms in Renal Cell Carcinoma Progression and Overall Survival: The Link to Plasma Circulating MiR-7 and MiR-221\/222 Expression. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0103258"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.2217\/fon-2019-0067","article-title":"Everolimus resistance in clear cell renal cell carcinoma: miRNA-101 and HIF-2\u03b1 as molecular triggers?","volume":"15","author":"Nogueira","year":"2019","journal-title":"Futur. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dias, F., Teixeira, A.L., Nogueira, I., Morais, M., Maia, J., Bodo, C., Ferreira, M., Silva, A., Vilhena, M., and Lobo, J. (2020). 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, 12.","DOI":"10.3390\/cancers12061450"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.eururo.2015.08.007","article-title":"Hypoxia, Hypoxia-inducible Transcription Factors, and Renal Cancer","volume":"69","author":"Grampp","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s00018-015-2070-4","article-title":"Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression","volume":"73","author":"Li","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrc3038","article-title":"Otto Warburg\u2019s contributions to current concepts of cancer metabolism","volume":"11","author":"Koppenol","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1016\/j.bbagen.2017.05.028","article-title":"MicroRNAs and altered metabolism of clear cell renal cell carcinoma: Potential role as aerobic glycolysis biomarkers","volume":"1861","author":"Morais","year":"2017","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3772","DOI":"10.3892\/ol.2016.4468","article-title":"Downregulating microRNA-144 mediates a metabolic shift in lung cancer cells by regulating GLUT1 expression","volume":"11","author":"Liu","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4245","DOI":"10.7314\/APJCP.2014.15.10.4245","article-title":"miR-186 Regulates Glycolysis through Glut1 During the Formation of Cancer-associated Fibroblasts","volume":"15","author":"Sun","year":"2014","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1159\/000484395","article-title":"Mir-144-3p Promotes Cell Proliferation, Metastasis, Sunitinib Resistance in Clear Cell Renal Cell Carcinoma by Downregulating ARID1A","volume":"43","author":"Xiao","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1158\/0008-5472.CAN-12-2651","article-title":"miR-186 Downregulation Correlates with Poor Survival in Lung Adenocarcinoma, Where It Interferes with Cell-Cycle Regulation","volume":"73","author":"Cai","year":"2013","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1097\/PPO.0000000000000106","article-title":"Drivers of the Warburg Phenotype","volume":"21","author":"Cairns","year":"2015","journal-title":"Cancer J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1200\/JCO.2018.79.2309","article-title":"Metabolic Pathways in Kidney Cancer: Current Therapies and Future Directions","volume":"36","author":"Rathmell","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.semnephrol.2018.01.006","article-title":"Metabolomics and Metabolic Reprogramming in Kidney Cancer","volume":"38","author":"Weiss","year":"2018","journal-title":"Semin. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e224","DOI":"10.1038\/oncsis.2016.35","article-title":"MiR-186 inhibited aerobic glycolysis in gastric cancer via HIF-1\u03b1 regulation","volume":"5","author":"Liu","year":"2016","journal-title":"Oncogenesis"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.bbrc.2016.10.004","article-title":"miR-144-3p serves as a tumor suppressor for renal cell carcinoma and inhibits its invasion and metastasis by targeting MAP3K8","volume":"480","author":"Liu","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","first-page":"186","article-title":"MiR-144 inhibits cell proliferation of renal cell carcinoma by targeting MTOR","volume":"36","author":"Xiang","year":"2016","journal-title":"Acta Acad. Med. Wuhan"},{"key":"ref_28","first-page":"249","article-title":"MicroRNA-186 Suppresses Cell Proliferation and Metastasis Through Targeting Sentrin-Specific Protease 1 in Renal Cell Carcinoma","volume":"26","author":"Jiao","year":"2018","journal-title":"Oncol. Res. Featur. Preclin. Clin. Cancer Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.tibs.2012.08.003","article-title":"Extracellular miRNAs: The mystery of their origin and function","volume":"37","author":"Turchinovich","year":"2012","journal-title":"Trends Biochem. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Collares, C.V.A., Evangelista, A.F., Xavier, D.J., Rassi, D.M., Arns, T., Foss-Freitas, M.C., Foss, M.C., Puthier, D., Sakamoto-Hojo, E.T., and A Passos, G. (2013). Identifying common and specific microRNAs expressed in peripheral blood mononuclear cell of type 1, type 2, and gestational diabetes mellitus patients. BMC Res. Notes, 6.","DOI":"10.1186\/1756-0500-6-491"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s12012-015-9329-8","article-title":"Biomarkers Associated with Ischemic Stroke in Diabetes Mellitus Patients","volume":"16","author":"Yang","year":"2015","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1007\/s00125-019-05014-5","article-title":"Extracellular vesicles in metabolic disease","volume":"62","author":"Akbar","year":"2019","journal-title":"Diabetologia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.mam.2017.11.010","article-title":"Extracellular vesicles in obesity and diabetes mellitus","volume":"60","author":"Pardo","year":"2018","journal-title":"Mol. Asp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1111\/cas.13722","article-title":"Regulation of antitumor miR-144-5p targets oncogenes: Direct regulation of syndecan-3 and its clinical significance","volume":"109","author":"Yamada","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_35","first-page":"D148","article-title":"miRTarBase 2020: Updates to the experimentally validated microRNA\u2013target interaction database","volume":"48","author":"Huang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"109428","DOI":"10.1016\/j.biopha.2019.109428","article-title":"Functions and mechanisms of miR-186 in human cancer","volume":"119","author":"Wang","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-016-0565-8","article-title":"Choosing the right cell line for renal cell cancer research","volume":"15","author":"Brodaczewska","year":"2016","journal-title":"Mol. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/S1357-2725(03)00040-2","article-title":"Regulation of proximal tubular epithelial cell CD44-mediated binding and internalisation of hyaluronan","volume":"35","author":"Jones","year":"2003","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/7\/1733\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:26:21Z","timestamp":1760361981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/7\/1733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,6]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["cancers13071733"],"URL":"https:\/\/doi.org\/10.3390\/cancers13071733","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,6]]}}}