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Cancer Cells' Metabolism Dynamics in Renal Cell Carcinoma Patients' Outcome: Influence of GLUT-1-Related hsa-miR-144
Mariana Morais1,2,3, Francisca Dias1,2, Inês Nogueira1,2,3
1Molecular 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.
Abstract:
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.
Insights
This study explored microRNAs (miRNAs) as potential biomarkers for clear cell renal cell carcinoma (ccRCC). Circulating levels of hsa-miR-144-5p and hsa-miR-186-3p correlate with ccRCC progression and patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Renal cell carcinoma (RCC) is a lethal kidney cancer with limited diagnostic biomarkers.
- Cancer cell metabolism, particularly glycolysis, is altered in RCC, involving proteins like glucose transporter 1 (GLUT-1).
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in cancer development.
Purpose of the Study:
- To investigate the potential of hsa-miR-144-5p and hsa-miR-186-3p as biomarkers for clear cell RCC (ccRCC).
- To establish the role of these miRNAs in ccRCC glycolysis.
- To correlate circulating miRNA levels with ccRCC clinical stages and patient prognosis.
Main Methods:
- Analysis of intracellular and extracellular miRNA levels in ccRCC cell lines.
- Assessment of GLUT-1 mRNA and protein expression.
- Measurement of glucose consumption and lactate production as glycolysis markers.
- Liquid biopsy approach to quantify circulating miRNA levels in RCC patients and healthy individuals.
Main Results:
- Decreased intracellular and increased extracellular levels of hsa-miR-144-5p and hsa-miR-186-3p were observed in ccRCC cells.
- Elevated GLUT-1 levels and enhanced glycolysis markers correlated with miRNA changes.
- RCC patients showed higher plasma levels of hsa-miR-186-3p compared to healthy controls.
- Higher hsa-miR-144-5p levels were associated with early ccRCC stages.
- Low hsa-miR-144-5p and high hsa-miR-186-3p plasma levels predicted worse overall survival.
Conclusions:
- Circulating hsa-miR-144-5p and hsa-miR-186-3p show potential as prognostic biomarkers for ccRCC.
- These miRNAs are linked to altered glycolysis in ccRCC.
- Further validation is needed for clinical application in ccRCC diagnosis and prognosis.
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