miR-24 suppression of POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) protects endothelial cell from diabetic damage.

Yan-Xiang Cui, Yu-Zhong Hua, Ning Wang, Xun Chen, Fang Wang, Jun-Ying Liu, Lei-Lei Wang, Chang-You Yan, Yang-Guo Ma, Yun-He Cao, Xiu-Hua Zhang

Biochemical and biophysical research communications 2016 Nov 25

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The regulatory transcriptional factor PATZ1 is abnormally up-regulated in diabetic endothelial cells (ECs) where it acts as an anti-angiogenic factor via modulation of fatty acid-binding protein 4 (FABP4) signaling. The aim of the present work was to elucidate the upstream molecular events regulating PATZ1 expression in diabetic angiogenesis. The bioinformatics search for microRNAs (miRNAs) able to potentially target PATZ1 led to the identification of several miRNAs. Among them we focused on the miR-24 since the multiple targets of miR-24, which have so far been identified in beta cells, cardiomyocytes and macrophages, are all involved in diabetic complications. miR-24 expression was significantly impaired in the ECs isolated from diabetic hearts. Functionally, endothelial migration was profoundly inhibited by miR-24 suppression in Ctrl ECs, whereas miR-24 overexpression by mimics treatment effectively restored the migration rate in diabetic ECs. Mechanistically, miR-24 directly targeted the 3'untranslated region (3'UTR) of PATZ1, and miR-24 accumulation potentiated endothelial migration by reducing the mRNA stability of PATZ1. Together, these results suggest a novel mechanism regulating endothelial PATZ1 expression based on the down-regulation of miR-24 expression caused by hyperglycemia. Interfering with PATZ1 expression via miRNAs or miRNA mimics could potentially represent a new way to target endothelial PATZ1-dependent signaling of vascular dysfunction in diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Citation

Yan-Xiang Cui, Yu-Zhong Hua, Ning Wang, Xun Chen, Fang Wang, Jun-Ying Liu, Lei-Lei Wang, Chang-You Yan, Yang-Guo Ma, Yun-He Cao, Xiu-Hua Zhang. miR-24 suppression of POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) protects endothelial cell from diabetic damage. Biochemical and biophysical research communications. 2016 Nov 25;480(4):682-689