Genomics

Dataset Information

154

NRF2 Controls Endothelial Plasticity with miR-93


ABSTRACT: Here we studied the role of oxidized phospholipids in mediating phenotype switching of endothelial cells between quiescent and angiogenic states. Two oxPAPC datasets, a microRNA array and global run-on sequencing (GRO-seq), was combined with Nuclear factor erythroid 2-Related Factor 2 (NRF2) binding model to select candidate miRNAs for further studies. The pre-screening resulted in a selection of miR-106b~25 cluster for further studies. The cluster was shown to be both oxPAPC-responsive and NRF2-regulated, and its diagnostic and prognostic potential was investigated in pericardial fluid samples of heart failure and atherosclerosis patients. As the most abundant member of the cluster in both endothelial cells and pericardial fluid of atherosclerosis patients, miR-93-5p was selected for more detailed studies. RNA-seq from miR-93 overexpressing cells revealed significant changes in pathways related to angiogenesis. Together with NRF2, miR-93 was shown to control endothelial plasticity through regulation of the key players, namely Krüppel-like factor 2 (KLF2) for quiescence, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) for glycolysis, and Vascular Endothelial Growth Factor A (VEGFA), Forkhead box protein O1 (FOXO1) and MYC proto-oncogene protein (MYC) for growth and proliferation.The findings show that NRF2 and miR-93 control the activity of endothelial cells and mediate the effects of oxPAPC on endothelial activation, collectively providing novel mechanisms for the control of endothelial plasticity and oxPAPC response. Overall design: Two samples. Human umbilical vein endothelial cells, control vs oxPAPC 6h

INSTRUMENT(S): Illumina HiSeq 2000 (Homo sapiens)

SUBMITTER: Minna U Kaikkonen  

PROVIDER: GSE103530 | GEO | 2017-11-01

SECONDARY ACCESSION(S): PRJNA401817

REPOSITORIES: GEO

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Publications

NRF2 regulates endothelial glycolysis and proliferation with miR-93 and mediates the effects of oxidized phospholipids on endothelial activation.

Kuosmanen Suvi M SM   Kansanen Emilia E   Kaikkonen Minna U MU   Sihvola Virve V   Pulkkinen Kati K   Jyrkkänen Henna-Kaisa HK   Tuoresmäki Pauli P   Hartikainen Juha J   Hippeläinen Mikko M   Kokki Hannu H   Tavi Pasi P   Heikkinen Sami S   Levonen Anna-Liisa AL  

Nucleic acids research 20180201 3


Phospholipids, such as 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC), are the major components of cell membranes. Their exposure to reactive oxygen species creates oxidized phospholipids, which predispose to the development of chronic inflammatory diseases and metabolic disorders through endothelial activation and dysfunction. Although the effects of oxidized PAPC (oxPAPC) on endothelial cells have been previously studied, the underlying molecular mechanisms evoking biological re  ...[more]

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