Abstract
BackgroundHypertrophic scar (HTS) is a fibrotic disorder of skins and may have repercussions on the appearance as well as functions of patients. Recent studies related have shown that competitive endogenous RNA (ceRNA) networks centering around miRNAs may play an influential role in HTS formation. This study aimed to construct and validate a three-miRNA (miR-422a, miR-2116-3p, and miR-3187-3p) ceRNA network, and explore its potential functions.MethodsQuantitative real‑time PCR (qRT‑PCR) was used to compare expression levels of miRNAs, lncRNAs, and genes between HTS and normal skin. Target lncRNAs and genes of each miRNA were predicted using starBase as well as TargetScan database to construct a distinct ceRNA network; overlapping target lncRNAs and genes of the three miRNAs were utilized to develop a three-miRNA ceRNA network. For every network, protein–protein interaction (PPI) network analysis was performed to identify its hub genes. For each network and its hub genes, Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to explore their possible functions.ResultsMiR-422a, miR-2116-3p, and miR-3187-3p were all downregulated in HTS tissues and fibroblasts. MiR-422a-based ceRNA network consisted of 101 lncRNAs with 133 genes; miR-2116-3p-centered ceRNA network comprised 85 lncRNAs and 978 genes; miR-3187-3p-derived ceRNA network encompassed 84 lncRNAs as well as 1128 genes. The three-miRNA ceRNA network included 2 lncRNAs with 9 genes, where MAPK1, FOSL2, ABI2, KPNA6, CBL, lncRNA-KCNQ1OT1, and lncRNA-EBLN3P were upregulated. According to GO and KEGG analysis, these networks were consistently related to ubiquitination. Three ubiquitination-related genes (CBL, SMURF2, and USP4) were upregulated and negatively correlated with the expression levels of the three miRNAs in HTS tissues.ConclusionsThis study identified a three-miRNA ceRNA network, which might take part in HTS formation and correlate with ubiquitination.
Highlights
Hypertrophic scar (HTS) is a fibrotic disorder of skins and may have repercussions on the appearance as well as functions of patients
Results miR‐422a, miR‐2116‐3p, and miR‐3187‐3p are downregulated in HTS tissues and fibroblasts To compare expression levels of miR-422a, miR-2116-3p, and miR-3187-3p between HTS and normal skin, 10 HTS tissues as well as normal skin samples were subject to quantitative real-time PCR (qRT-PCR)
These findings suggest that miR-422a, miR-2116-3p, and miR3187-3p may have a close relationship with HTS formation, and play a protective role in the process
Summary
Hypertrophic scar (HTS) is a fibrotic disorder of skins and may have repercussions on the appearance as well as functions of patients. Hypertrophic scar (HTS) is a fibro-proliferative disease, charactered by excessive proliferation of fibroblasts, activation of myofibroblasts, and deposition of extracellular matrix (ECM). This disorder has the potential to cause disfiguration and dysfunction in facial areas and joints, which may take a heavy toll on the physical and psychological condition of patients. In a preliminary microarray test, miR-422a, miR-2116-3p, and miR-3187-3p have been discovered to be downregulated in HTS tissues (fold change > 2 and P < 0.05) [8] These studies have suggested that the three miRNAs may correlate with HTS formation and contribute positively to alleviating HTS. Their expression patterns remain validated in tissues as well as fibroblasts, and their roles in HTS pathogenesis need to be answered
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