Long non-coding RNA HOXA11-AS induces type I collagen synthesis to stimulate keloid formation via sponging miR-124-3p and activation of Smad5 signaling

Keloid, characterized by exuberant collagen deposition and invasive growth beyond original wound margins, results from abnormal wound healing. A recent microarray analysis identified homeobox (HOX) A11 antisense (HOXA11-AS) as a keloid-specific long non-coding RNA, although its potential role in kel...

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Bibliographic Details
Published in:American Journal of Physiology: Cell Physiology 2019-11, Vol.317 (5), p.C1001-C1010
Main Authors: Jin, Jun, Zhai, Hong-Feng, Jia, Zhen-Hua, Luo, Xiao-Hua
Format: Article
Language:English
Subjects:
Cell Proliferation - physiology
Cells, Cultured
Collagen Type I - biosynthesis
Collagen Type I - genetics
Homeodomain Proteins - biosynthesis
Homeodomain Proteins - genetics
Humans
Keloid - genetics
Keloid - metabolism
Keloid - pathology
MicroRNAs - genetics
MicroRNAs - metabolism
RNA, Long Noncoding - biosynthesis
RNA, Long Noncoding - genetics
Smad5 Protein - genetics
Smad5 Protein - metabolism
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Summary:Keloid, characterized by exuberant collagen deposition and invasive growth beyond original wound margins, results from abnormal wound healing. A recent microarray analysis identified homeobox (HOX) A11 antisense (HOXA11-AS) as a keloid-specific long non-coding RNA, although its potential role in keloid formation remains elusive. In this study, hematoxylin-eosin, Masson, and immunohistochemical staining of type I collagen (ColI) revealed abnormal arrangement and hyperplasia of fibers in keloid tissues along with increased ColI level. qRT-PCR and Western blot showed that HOXA11-AS and ColI were significantly upregulated, while miR-124-3p was decreased in both keloid tissues and human keloid fibroblasts (HKFs). Knockdown of HOXA11-AS inhibited cell proliferation (by CCK-8 and immunofluorescence staining of Ki67) and cell migration (by wound healing and transwell assays). Mechanistic experiments verified that HOXA11-AS acted as a sponge of micro-RNA (miR)-124-3p and Smad5 was a target of miR-124-3p. miR-124-3p sufficiently reversed the regulatory effects of HOXA11-AS, and Smad5 was involved in miR-124-3p-mediated biological functions. Furthermore, HOXA11-AS induced ColI synthesis via sponging miR-124-3p-mediated Smad5 signaling, thus promoting keloid formation. Overall, our study implied that HOXA11-AS induces ColI synthesis to promoted keloid formation via sponging miR-124-3p-mediated Smad5 signaling, which might offer a novel target for developing the therapy of keloid formation.
ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.00319.2018