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

被引:41
作者
Jin, Jun [1 ]
Zhai, Hong-Feng [1 ]
Jia, Zhen-Hua [1 ]
Luo, Xiao-Hua [1 ]
机构
[1] Zhengzhou Univ Peoples Hosp, Henan Prov Peoples Hosp, Dept Plast Surg, 7 Weiwu Rd, Zhengzhou 450000, Henan, Peoples R China
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2019年 / 317卷 / 05期
关键词
keloid formation; lncRNA HOXA11-AS; miR-124-3p; Smad5; type I collagen; EXPRESSION; FIBROBLASTS; PATHOGENESIS; PATHWAYS; INVASION; GROWTH; CANCER; SCARS;
D O I
10.1152/ajpcell.00319.2018
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:C1001 / C1010
页数:10
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