MicroRNAs and altered metabolism of clear cell renal cell carcinoma: Potential role as aerobic glycolysis biomarkers

Biochim Biophys Acta Gen Subj. 2017 Sep;1861(9):2175-2185. doi: 10.1016/j.bbagen.2017.05.028. Epub 2017 Jun 1.

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.

Keywords: Aerobic glycolysis; Renal cell carcinoma; Warburg effect; microRNAs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aerobiosis
  • Biomarkers
  • Carcinoma, Renal Cell / metabolism*
  • Citric Acid Cycle
  • Fluorodeoxyglucose F18
  • Gene Expression Regulation, Neoplastic
  • Glucose Transporter Type 1 / physiology
  • Glucose Transporter Type 4 / physiology
  • Glycolysis*
  • Humans
  • Kidney Neoplasms / metabolism*
  • MicroRNAs / physiology*
  • Positron-Emission Tomography

Substances

  • Biomarkers
  • Glucose Transporter Type 1
  • Glucose Transporter Type 4
  • MicroRNAs
  • Fluorodeoxyglucose F18