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  MicroRNA-Mediated Metabolic Reprograming in Renal Cancer

Bogusławska, J., Popławski, P., Alseekh, S., Koblowska, M., Iwanicka-Nowicka, R., Rybicka, B., et al. (2019). MicroRNA-Mediated Metabolic Reprograming in Renal Cancer. Cancers, 11(12): 1825. doi:10.3390/cancers11121825.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-3F61-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-3F62-7
Genre: Journal Article

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Bogusławska, Joanna1, Author
Popławski, Piotr1, Author
Alseekh, S.2, Author              
Koblowska, Marta1, Author
Iwanicka-Nowicka, Roksana1, Author
Rybicka, Beata1, Author
Kędzierska, Hanna1, Author
Głuchowska, Katarzyna1, Author
Hanusek, Karolina1, Author
Tański, Zbigniew1, Author
Fernie, A. R.2, Author              
Piekiełko-Witkowska, Agnieszka1, Author
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1External Organizations, ou_persistent22              
2Central Metabolism, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society, ou_1753339              

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 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 gt;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 ldquo;metabomiRsrdquo; that target genes of crucial metabolic pathways (PPP (the pentose phosphate pathway), TCA cycle, and arginine metabolism).

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Language(s): eng - English
 Dates: 2019
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: DOI: 10.3390/cancers11121825
BibTex Citekey: cancers11121825
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Title: Cancers
Source Genre: Journal
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Pages: - Volume / Issue: 11 (12) Sequence Number: 1825 Start / End Page: - Identifier: ISSN: 2072-6694