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Prognostic Implication of pAMPK Immunohistochemical Staining by Subcellular Location and Its Association with SMAD Protein Expression in Clear Cell Renal Cell Carcinoma

MicroRNA-Mediated Metabolic Reprograming in Renal Cancer

Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, ul. Marymoncka 99/103, 01-813 Warsaw, Poland
Max-Planck Institute of Molecular Plant Physiology, 14476 Potsdam-Golm, Germany
Center for Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
Laboratory of Systems Biology, Faculty of Biology, University of Warsaw, 02-106 Warsaw, Poland
Laboratory for Microarray Analysis, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland
Masovian Specialist Hospital in Ostroleka, 07-410 Ostroleka, Poland
Author to whom correspondence should be addressed.
Present affiliation of HK: Laboratory of Experimental Medicine, Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland.
Cancers 2019, 11(12), 1825;
Received: 25 October 2019 / Accepted: 15 November 2019 / Published: 20 November 2019
(This article belongs to the Special Issue Renal Cell Carcinoma)
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). View Full-Text
Keywords: renal cell cancer; microRNA; metabolome; proliferation; PPP; pentose phosphate pathway; TCA cycle; miR-155-5p; miR-146a-5p; TCGA renal cell cancer; microRNA; metabolome; proliferation; PPP; pentose phosphate pathway; TCA cycle; miR-155-5p; miR-146a-5p; TCGA
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MDPI and ACS Style

Bogusławska, J.; Popławski, P.; Alseekh, S.; Koblowska, M.; Iwanicka-Nowicka, R.; Rybicka, B.; Kędzierska, H.; Głuchowska, K.; Hanusek, K.; Tański, Z.; Fernie, A.R.; Piekiełko-Witkowska, A. MicroRNA-Mediated Metabolic Reprograming in Renal Cancer. Cancers 2019, 11, 1825.

AMA Style

Bogusławska J, Popławski P, Alseekh S, Koblowska M, Iwanicka-Nowicka R, Rybicka B, Kędzierska H, Głuchowska K, Hanusek K, Tański Z, Fernie AR, Piekiełko-Witkowska A. MicroRNA-Mediated Metabolic Reprograming in Renal Cancer. Cancers. 2019; 11(12):1825.

Chicago/Turabian Style

Bogusławska, Joanna, Piotr Popławski, Saleh Alseekh, Marta Koblowska, Roksana Iwanicka-Nowicka, Beata Rybicka, Hanna Kędzierska, Katarzyna Głuchowska, Karolina Hanusek, Zbigniew Tański, Alisdair R. Fernie, and Agnieszka Piekiełko-Witkowska. 2019. "MicroRNA-Mediated Metabolic Reprograming in Renal Cancer" Cancers 11, no. 12: 1825.

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