Morais Mariana, Dias Francisca, Nogueira Inês, Leão Anabela, Gonçalves Nuno, Araújo Luís, Granja Sara, Baltazar Fátima, Teixeira Ana L, Medeiros Rui
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.
ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal.
Cancers (Basel). 2021 Apr 6;13(7):1733. doi: 10.3390/cancers13071733.
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.
由于包括葡萄糖转运蛋白1（GLUT-1）在内的关键蛋白失调，癌细胞的代谢发生改变，其mRNA水平受微小RNA（miRNA）影响。肾细胞癌（RCC）是成人肾脏中最常见且致命的肿瘤，主要原因是缺乏准确的诊断和随访生物标志物。作为一种与代谢相关的癌症，本研究旨在了解hsa-miR-144-5p和hsa-miR-186-3p作为透明细胞肾细胞癌（ccRCC）生物标志物的潜力，确定它们在其糖酵解状态中的作用。使用三种ccRCC细胞系，评估了这两种miRNA的细胞内和细胞外水平、GLUT-1的mRNA表达和蛋白水平。将葡萄糖消耗和乳酸产生作为糖酵解标志物进行评估。观察到这些miRNA的细胞内水平降低及其排泄增加，同时伴有GLUT-1水平和糖酵解标志物的增加。通过液体活检方法，我们发现RCC患者的血浆hsa-miR-186-3p水平高于健康个体。hsa-miR144-5p水平较高与临床早期相关。当根据miRNA血浆水平对患者进行分层时，hsa-miR-144-5p血浆水平低和hsa-miR-186-3p血浆水平高（高危组）的患者总生存期最差。因此，这些miRNA的循环水平可能是ccRCC预后的潜在生物标志物。
