1. Long non-coding RNA HOXA11-AS accelerates the progression of keloid formation via miR-124-3p/TGFβR1 axis
- Author
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Zhen-Hua Jia, Xiao-Hua Luo, Hong-Feng Zhai, and Jun Jin
- Subjects
Adult ,Male ,0301 basic medicine ,Angiogenesis ,Receptor, Transforming Growth Factor-beta Type I ,Down-Regulation ,Neovascularization, Physiologic ,Apoptosis ,Biology ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,Keloid ,medicine ,Humans ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Tube formation ,Base Sequence ,Akt/PKB signaling pathway ,Cell Biology ,Fibroblasts ,Middle Aged ,medicine.disease ,Long non-coding RNA ,Up-Regulation ,Cell biology ,MicroRNAs ,Phenotype ,030104 developmental biology ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,RNA, Long Noncoding ,Proto-Oncogene Proteins c-akt ,Signal Transduction ,Research Paper ,Developmental Biology ,Transforming growth factor - Abstract
Emerging evidence reveals the importance of long non-coding RNAs (lncRNAs) in the development and progression of keloid formation, whereas the underlying mechanisms are not well understood. In the present study, we investigated the biological effects and molecular mechanisms of lncRNA HOXA11-AS in keloid formation. First, the expression levels of HOXA11-AS, miR-124-3p, and transforming growth factor β receptor type I (TGFβR1) were measured in both keloid tissues and human keloid fibroblasts (HKFs) using qRT-PCR and western blot analysis, respectively. Next, we adopted both gain- and loss-of-function strategies to explore the significance of HOXA11-AS. TUNEL, flow cytometry, DNA ladder, and tube formation assays were performed to measure cell apoptosis and angiogenesis, respectively. Besides, the potential binding relationship between HOXA11-AS and miR-124-3p, as well as miR-124-3p and TGFβR1 was identified using bioinformatic screening and verified by luciferase reporter assay. Furthermore, we explored the importance of miR-124-3p in HOXA11-AS-induced phenotypes and regulations on TGFβ signaling or PI3K/Akt signaling. We found that HOXA11-AS and TGFβR1 were significantly up-regulated, while miR-124-3p was down-regulated both in keloid tissues or fibroblasts than in normal skin tissues or fibroblasts. Functionally, high expression of HOXA11-AS essentially inhibited cell apoptosis and promoted fibroblast-induced angiogenesis. Mechanistically, miR-124-3p was identified as a downstream effector to be involved in HOXA11-AS-mediated phenotypes through directly targeting TGFβR1, thus modulating PI3K/Akt signaling pathway. Taken together, our findings revealed that HOXA11-AS inhibits cell apoptosis and promotes angiogenesis through miR-124-3p/TGFβR1 axis, contributing to the progression of keloid formation, which might provide a novel target for keloid therapy.
- Published
- 2019