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Published on: November 30, 2013
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.
Abstract:
Metabolic reprogramming is one of the hallmarks of renal cell cancer (RCC). We hypothesized that altered metabolism of RCC cells results from dysregulation of microRNAs targeting metabolically relevant genes. Combined large-scale transcriptomic and metabolic analysis of RCC patients tissue samples revealed a group of microRNAs that contribute to metabolic reprogramming in RCC. miRNAs expressions correlated with their predicted target genes and with gas chromatography-mass spectrometry (GC-MS) metabolome profiles of RCC tumors. Assays performed in RCC-derived cell lines showed that miR-146a-5p and miR-155-5p targeted genes of PPP (the pentose phosphate pathway) (G6PD and TKT), the TCA (tricarboxylic acid cycle) cycle (SUCLG2), and arginine metabolism (GATM), respectively. miR-106b-5p and miR-122-5p regulated the NFAT5 osmoregulatory transcription factor. Altered expressions of G6PD, TKT, SUCLG2, GATM, miR-106b-5p, miR-155-5p, and miR-342-3p correlated with poor survival of RCC patients. miR-106b-5p, miR-146a-5p, and miR-342-3p stimulated proliferation of RCC cells. The analysis involving >6000 patients revealed that miR-34a-5p, miR-106b-5p, miR-146a-5p, and miR-155-5p are PanCancer metabomiRs possibly involved in global regulation of cancer metabolism. In conclusion, we found that microRNAs upregulated in renal cancer contribute to disturbed expression of key genes involved in the regulation of RCC metabolome. miR-146a-5p and miR-155-5p emerge as a key "metabomiRs" that target genes of crucial metabolic pathways (PPP (the pentose phosphate pathway), TCA cycle, and arginine metabolism).
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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