Abstract
Background
Breast cancer (BC) is the second leading cause of cancer-related mortality among women. Beyond the established tumourigenic role of genetic mutations, metabolic reprogramming is another key cancer hallmark. Glucose metabolism in particular is known to be prominently altered in tumours, in order to support biomass accumulation and cancer cell survival. The tumor suppressor microRNA (miRNA) miR-22 has been previously associated with a plethora of BC phenotypes such as growth, invasion-metastasis, and regulation of metabolic phenotypes such as lipid and folate metabolism. In this study, we aimed to investigate the role of miR-22 in the regulation of glucose metabolism in BC cells.
Methods and results
Here we examined how miR-22 affects glucose metabolism in the MCF-7 BC cells. We found that over-expression of miR-22 caused a reduced glycolytic rate in these cells. Moreover, the miRNA also rendered MCF-7 cells more sensitive to lower glucose levels. We next unbiasedly screened the transcript levels of 84 genes relevant to glucose metabolism using the Human Glucose RT2 Profiler PCR Array. Interestingly, the strongest effect identified by this screen was the upregulation of genes involved in glycogen synthesis and the repression of gene involved in glycogen catabolism. Examination of publicly available transcriptomic datasets confirmed the correlations between expression of miR-22 and these glycogen metabolism genes in BC cells.
Conclusion
This study has generated evidence for a regulatory role of miR-22 in glucose and glycogen metabolism, expanding the involvement of this miRNA in BC metabolic reprogramming.
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Data Availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- miRNA:
-
microRNA
- BC:
-
Breast cancer
- miR22HG:
-
miR-22 host gene
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Funding
HK, CK, and JE acknowledge support by the European Community’s Seventh Framework Programme—Health (FP7/2007–2013) project DETECTIVE (grant agreement number 266838).
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Conceptualization: Costas Koufaris, Hector C Keun; Methodology: Costas Koufaris, Margarita E Papandreou, James K Ellis, Vicky Nicolaidou, Hector C Keun; Formal analysis and investigation: Costas Koufaris; Writing - original draft preparation: Costas Koufaris, Vicky Nicolaidou; Writing - review and editing: Costas Koufaris, Margarita E Papandreou, James K Ellis, Vicky Nicolaidou, Hector C Keun; Funding acquisition: Hector C Keun; Resources: Hector C Keun; Supervision: Costas Koufaris, Hector C Keun.
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Koufaris, C., Papandreou, M.E., Ellis, J.K. et al. miR-22-enriched breast cancer cells display repressed glycolytic metabolism, increased glycogen synthesis, and reduced survival in low glucose conditions. Mol Biol Rep 50, 5185–5193 (2023). https://doi.org/10.1007/s11033-023-08458-6
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DOI: https://doi.org/10.1007/s11033-023-08458-6