Mariana Morais1, Francisca Dias2, Ana L Teixeira3, Rui Medeiros4. 1. Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal; ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Portugal. 2. Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal; ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Portugal; Research Department, LPCC-Portuguese League, Against Cancer (NRNorte), Porto, Portugal. 3. Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal; Research Department, LPCC-Portuguese League, Against Cancer (NRNorte), Porto, Portugal. Electronic address: ana.luisa.teixeira@ipoporto.min-saude.pt. 4. Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal; Research Department, LPCC-Portuguese League, Against Cancer (NRNorte), Porto, Portugal; CEBIMED, Faculty of Health Sciences, Fernando Pessoa University, Porto, Portugal; FMUP, Faculty of Medicine, University of Porto, Portugal. Electronic address: ruimedei@ipoporto.min-saude.pt.
Abstract
BACKGROUND: Warburg Effect is a metabolic switch that occurs in most of cancer cells but its advantages are not fully understood. This switch is known to happen in renal cell carcinoma (RCC), which is the most common solid cancer of the adult kidney. RCC carcinogenesis is related to pVHL loss and Hypoxia Inducible Factor (HIF) activation, ultimately leading to the activation of several genes related to glycolysis. MicroRNAs (miRNAs) regulate gene expression at a post-transcriptional level and are also deregulated in several cancers, including RCC. SCOPE OF REVIEW: This review focuses in the miRNAs that direct target enzymes involved in glycolysis and that are deregulated in several cancers. It also reviews the possible application of miRNAs in the improvement of clinical patients' management. MAJOR CONCLUSIONS: Several miRNAs that direct target enzymes involved in glycolysis are downregulated in cancer, strongly influencing the Warburg Effect. Due to this strong influence, FDG-PET can possibly benefit from measurement of these miRNAs. Restoring their levels can also bring an improvement to the current therapies. GENERAL SIGNIFICANCE: Despite being known for almost a hundred years, the Warburg Effect is not fully understood. MiRNAs are now known to be intrinsically connected with this effect and present an opportunity to understand it. They also open a new door to improve current diagnosis and prognosis tests as well as to complement current therapies. This is urgent for cancers like RCC, mostly due to the lack of an efficient screening test for early relapse detection and follow-up and the development of resistance to current therapies.
BACKGROUND: Warburg Effect is a metabolic switch that occurs in most of cancer cells but its advantages are not fully understood. This switch is known to happen in renal cell carcinoma (RCC), which is the most common solid cancer of the adult kidney. RCC carcinogenesis is related to pVHL loss and Hypoxia Inducible Factor (HIF) activation, ultimately leading to the activation of several genes related to glycolysis. MicroRNAs (miRNAs) regulate gene expression at a post-transcriptional level and are also deregulated in several cancers, including RCC. SCOPE OF REVIEW: This review focuses in the miRNAs that direct target enzymes involved in glycolysis and that are deregulated in several cancers. It also reviews the possible application of miRNAs in the improvement of clinical patients' management. MAJOR CONCLUSIONS: Several miRNAs that direct target enzymes involved in glycolysis are downregulated in cancer, strongly influencing the Warburg Effect. Due to this strong influence, FDG-PET can possibly benefit from measurement of these miRNAs. Restoring their levels can also bring an improvement to the current therapies. GENERAL SIGNIFICANCE: Despite being known for almost a hundred years, the Warburg Effect is not fully understood. MiRNAs are now known to be intrinsically connected with this effect and present an opportunity to understand it. They also open a new door to improve current diagnosis and prognosis tests as well as to complement current therapies. This is urgent for cancers like RCC, mostly due to the lack of an efficient screening test for early relapse detection and follow-up and the development of resistance to current therapies.