鉴定和功能分析增生性瘢痕中的一个三 miRNA ceRNA 网络。

Identification and functional analysis of a three-miRNA ceRNA network in hypertrophic scars.

机构信息

Department of Plastic and Reconstructive Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200001, China.

出版信息

J Transl Med. 2021 Oct 29;19(1):451. doi: 10.1186/s12967-021-03091-y.

DOI:10.1186/s12967-021-03091-y

PMID:34715879

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8556926/

Abstract

BACKGROUND

Hypertrophic 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.

METHODS

Quantitative 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.

RESULTS

MiR-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.

CONCLUSIONS

This study identified a three-miRNA ceRNA network, which might take part in HTS formation and correlate with ubiquitination.

摘要

背景

增生性瘢痕（HTS）是一种皮肤纤维化疾病，可能会对患者的外观和功能产生影响。最近的相关研究表明，以 miRNA 为中心的竞争性内源 RNA（ceRNA）网络可能在 HTS 的形成中发挥重要作用。本研究旨在构建和验证一个三 miRNA（miR-422a、miR-2116-3p 和 miR-3187-3p）ceRNA 网络，并探讨其潜在功能。

方法

采用实时荧光定量 PCR（qRT-PCR）比较 HTS 和正常皮肤组织中 miRNA、lncRNA 和基因的表达水平。利用 starBase 和 TargetScan 数据库预测每个 miRNA 的靶 lncRNA 和基因，构建特定的 ceRNA 网络；利用三个 miRNA 的重叠靶 lncRNA 和基因构建三 miRNA ceRNA 网络。对每个网络进行蛋白质-蛋白质相互作用（PPI）网络分析，识别其枢纽基因。对每个网络及其枢纽基因进行基因肿瘤学（GO）和京都基因与基因组百科全书（KEGG）分析，探讨其可能的功能。

结果

miR-422a、miR-2116-3p 和 miR-3187-3p 在 HTS 组织和成纤维细胞中均下调。miR-422a 为基础的 ceRNA 网络包含 101 个 lncRNA 和 133 个基因；miR-2116-3p 为中心的 ceRNA 网络包含 85 个 lncRNA 和 978 个基因；miR-3187-3p 衍生的 ceRNA 网络包含 84 个 lncRNA 和 1128 个基因。三 miRNA ceRNA 网络包含 2 个 lncRNA 和 9 个基因，其中 MAPK1、FOSL2、ABI2、KPNA6、CBL、lncRNA-KCNQ1OT1 和 lncRNA-EBLN3P 上调。根据 GO 和 KEGG 分析，这些网络与泛素化密切相关。三个泛素化相关基因（CBL、SMURF2 和 USP4）上调，并与 HTS 组织中三个 miRNA 的表达水平呈负相关。