MicroRNA-Mediated Metabolic Reprograming in Renal Cancer

Joanna Bogusławska1, Piotr Popławski1, Saleh Alseekh2,3

  • 1Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, ul. Marymoncka 99/103, 01-813 Warsaw, Poland.

Cancers
|November 24, 2019
PubMed

Insights

MicroRNAs play a key role in renal cell cancer (RCC) metabolic reprogramming by targeting essential metabolic genes. Upregulated microRNAs like miR-146a-5p and miR-155-5p are linked to poor patient survival and cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Metabolomics

Background:

  • Metabolic reprogramming is a critical hallmark of renal cell cancer (RCC).
  • Dysregulation of microRNAs (miRNAs) targeting metabolic genes is hypothesized to drive altered RCC cell metabolism.

Purpose of the Study:

  • To investigate the role of microRNAs in the metabolic reprogramming of renal cell cancer.
  • To identify specific miRNAs and their target genes involved in RCC metabolism and patient outcomes.

Main Methods:

  • Combined large-scale transcriptomic and metabolomic (GC-MS) analysis of RCC patient tissues.
  • In vitro assays in RCC-derived cell lines to validate miRNA-target interactions.
  • Correlation analysis of miRNA and gene expression with patient survival data (>6000 patients).

Main Results:

  • Identified a group of miRNAs contributing to metabolic reprogramming in RCC.
  • miR-146a-5p and miR-155-5p were found to target key genes in the pentose phosphate pathway (PPP), tricarboxylic acid (TCA) cycle, and arginine metabolism.
  • Altered expression of specific miRNAs (miR-106b-5p, miR-146a-5p, miR-155-5p, miR-342-3p) and their target genes correlated with poor patient survival and stimulated RCC cell proliferation.
  • miR-34a-5p, miR-106b-5p, miR-146a-5p, and miR-155-5p were identified as potential PanCancer metabomiRs.

Conclusions:

  • Upregulated microRNAs in renal cancer contribute to disturbed expression of key metabolic genes.
  • miR-146a-5p and miR-155-5p are identified as key "metabomiRs" regulating crucial metabolic pathways in RCC.
  • These findings highlight the potential of targeting specific miRNAs for therapeutic strategies in renal cell cancer.

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