Down-regulation of long non-coding RNA HOTAIR promotes angiogenesis via regulating miR-126/SCEL pathways in burn wound healing

• Published in: Cell death & disease 2020-01, Vol.11 (1), p.61-61, Article 61
• Main Authors: Jiang, Bimei, Tang, Yuting, Wang, Hao, Chen, Cheng, Yu, Wenchang, Sun, Hui, Duan, Mengting, Lin, Xiaofang, Liang, Pengfei
• Format: Article
• Language: English
• Subjects: 13/109; 13/2; 13/31; 38/77; 38/91; 42/44; 631/80/84/2334; 692/699/578; Angiogenesis; Antibodies; Antisense RNA; Apoptosis; Apoptosis - genetics; Base Sequence; Biochemistry; Biomedical and Life Sciences; Burns - genetics; Burns - pathology; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Biology; Cell Culture; Cell growth; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cell Survival - genetics; Colorectal carcinoma; Dermis - metabolism; Dermis - pathology; DNA microarrays; Down-Regulation - genetics; Endothelial cells; Fluorescein isothiocyanate; Gene expression; Heat-Shock Response - genetics; HEK293 Cells; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Immunology; Keratinocytes; Life Sciences; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neovascularization, Pathologic - genetics; Non-coding RNA; Propidium iodide; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Thermal injury; Transcription; Umbilical vein; Up-Regulation - genetics; Wound healing; Wound Healing - genetics
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-2247-0

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.