MicroRNA-Mediated Metabolic Reprograming in Renal Cancer

被引：31

作者：

Boguslawska, Joanna ^{[1
]}

Poplawski, Piotr ^{[1
]}

Alseekh, Saleh ^{[2
,3
]}

Koblowska, Marta ^{[4
,5
]}

Iwanicka-Nowicka, Roksana ^{[4
,5
]}

Rybicka, Beata ^{[1
]}

Kedzierska, Hanna ^{[1
,7
]}

Gluchowska, Katarzyna ^{[1
]}

Hanusek, Karolina ^{[1
]}

Tanski, Zbigniew ^{[6
]}

Fernie, Alisdair R. ^{[2
,3
]}

Piekielko-Witkowska, Agnieszka ^{[1
]}

机构：

[1] Ctr Postgrad Med Educ, Dept Biochem & Mol Biol, Ul Marymoncka 99-103, PL-01813 Warsaw, Poland

[2] Max Planck Inst Mol Plant Physiol, D-14476 Potsdam, Germany

[3] Ctr Plant Syst Biol & Biotechnol, Plovdiv 4000, Bulgaria

[4] Univ Warsaw, Fac Biol, Lab Syst Biol, PL-02106 Warsaw, Poland

[5] Polish Acad Sci, Inst Biochem & Biophys, Lab Microarray Anal, PL-02106 Warsaw, Poland

[6] Masovian Specialist Hosp Ostroleka, PL-07410 Ostroleka, Poland

[7] Univ Warsaw, Ctr New Technol, Lab Expt Med, PL-02097 Warsaw, Poland

来源：

CANCERS | 2019年 / 11卷 / 12期

关键词：

renal cell cancer; microRNA; metabolome; proliferation; PPP; pentose phosphate pathway; TCA cycle; miR-155-5p; miR-146a-5p; TCGA; PENTOSE-PHOSPHATE PATHWAY; ADRENOMEDULLIN INFUSION; SURVIVAL; CELLS; HOMEOSTASIS; INHIBITION; CREATINE; VOLUME; GENE;

D O I：

10.3390/cancers11121825

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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).

引用

页数：21

共 58 条

[1] Predicting effective microRNA target sites in mammalian mRNAs [J].