Transcriptome analysis-identified long noncoding RNA CRNDE in maintaining endothelial cell proliferation, migration, and tube formation

Authors

Matthew Moran, University of Nebraska - LincolnFollow
Xiao Cheng Zeng, University of Nebraska-LincolnFollow
Mohamed Sham Shihabudeen Haider Ali, University of Nebraska-Lincoln
Nishikant Wase, University of Nebraska-LincolnFollow
Nghi Nguyen, University of Nebraska-Lincoln
Weilong Yang, University of Nebraska-LincolnFollow
Chi Zhang, University of Nebraska - LincolnFollow
Concetta C. DiRusso, University of Nebraska - LincolnFollow
Xinghui Sun, University of Nebraska - LincolnFollow

ORCID IDs

http://orcid.org/0000-0001-7388-9152

Citation

The Author(s) 2019

Comments

(2019) 9:19548 | https://doi.org/10.1038/s41598-019-56030-9

Abstract

Obesity is a leading risk factor for type-2 diabetes. Diabetes often leads to the dysregulation of angiogenesis, although the mechanism is not fully understood. Previously, long noncoding RNAs (lncRNAs) have been found to modulate angiogenesis. In this study, we asked how the expression levels of lncRNAs change in endothelial cells in response to excessive palmitic acid treatment, an obesitylike condition. Bioinformatics analysis revealed that 305 protein-coding transcripts were upregulated and 70 were downregulated, while 64 lncRNAs were upregulated and 46 were downregulated. Gene ontology and pathway analysis identified endoplasmic reticulum stress, HIF-1 signaling, and Toll-like receptor signaling as enriched after palmitic acid treatment. Moreover, we newly report enrichment of AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling, and cysteine and methionine metabolism by palmitic acid. One lncRNA, Colorectal Neoplasia Differentially Expressed (CRNDE), was selected for further investigation. Palmitic acid induces CRNDE expression by 1.9-fold. We observed that CRNDE knockdown decreases endothelial cell proliferation, migration, and capillary tube formation. These decreases are synergistic under palmitic acid stress. These data demonstrated that lncRNA CRNDE is a regulator of endothelial cell proliferation, migration, and tube formation in response to palmitic acid, and a potential target for therapies treating the complications of obesityinduced diabetes.