Abstract
miR-126, an endothelial-specific microRNA, is associated to vascular integrity and angiogenesis. It is well established that angiogenesis plays a critical role in burn wound healing. However, there was a lack of understanding of the mechanism by which miR-126 regulates angiogenesis during burn wound healing. HOX transcript antisense intergenic RNA (HOTAIR) is a well-characterized long non-coding RNA (lncRNA) involved in cell proliferation, apoptosis, migration, and invasion of cancer cells. Sciellin (SCEL), a precursor to the cornified envelope of human keratinocytes, has been shown to inhibit migration and invasion capabilities of colorectal cancer cells. In this study, a cohort of 20 burn wound tissues and paired adjacent normal tissues were collected. LncRNA and messenger RNA expression profiles were screened by microarray analysis in five pairs of samples with mostly increased miR-126 levels. miR-126 was highly expressed in burn wound tissues and human umbilical vein endothelial cells (HUVECs) exposed to heat stress, whereas HOTAIR and SCEL were down-regulated after thermal injury. Bioinformatic analysis, dual luciferase reporter assay, and quantitative real-time PCR were conducted to validate that HOTAIR and SCEL competitively bind to miR-126 to function as the competitive endogenous RNA. miR-126 promoted endothelial cell proliferation, migration, and angiogenesis, but suppressed apoptosis, while HOTAIR and SCEL exerted opposite effects in HUVECs. The biological functions were determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, Annexin-V-FITC/PI (propidium iodide/fluorescein isothiocyanate) staining, transwell migration, and tube formation assays. Collectively, our study revealed that HOTAIR/miR-126/SCEL axis contributes to burn wound healing through mediating angiogenesis.
Highlights
Burn injuries could be induced by thermal agents, as well as radiations or chemicals
Five pairs of samples with mostly increased miR-126 levels were selected for long non-coding RNA (lncRNA) microarray analysis
The results revealed 33,100 differentially expressed lncRNAs between these two groups, consisting of 19,600 lncRNAs up-regulated >1-fold in burn wound tissues compared to normal tissues, and 13,500 down-regulated lncRNAs
Summary
Burn injuries could be induced by thermal agents, as well as radiations or chemicals. Severe burn injuries induce complex pathologic effects on nearly every organ system, and lead to ~180,000 death annually worldwide[1]. The post-burn mortality has Official journal of the Cell Death Differentiation Association. Expressed microRNAs (miRNAs) were identified in burned tissues, including the known oncogenic miRNA miR-1266. Emerging evidence suggest that miR-126, which is highly expressed in endothelial cells, plays important roles in angiogenesis and maintenance of vascular integrity. In vessel injury or hypoxia, overexpression of miR-126 induces angiogenesis, while it maintains vascular homeostasis by inhibiting angiogenesis in adult organisms[10,11]. Microarray analysis revealed that SCEL was down-regulated in burned tissues, indicating that miR-126/SCEL might play an important role in burn wound healing
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