LncRNA ENST00000581911 Regulates Extraocular Muscle Remodeling by Interacting With KHSRP in Thyroid Eye Disease.

IF 5 2区医学 Q1 OPHTHALMOLOGY

Investigative ophthalmology & visual science Pub Date : 2025-03-03 DOI:10.1167/iovs.66.3.46

Mingsu Shi, Rongmei Zhou, Weiai Shen, Yu Liang, Yihan Zhang, Lingyun Liu, Runyi Shao, Yanxi Fang, Chen Zhao, Lianqun Wu

{"title":"LncRNA ENST00000581911 Regulates Extraocular Muscle Remodeling by Interacting With KHSRP in Thyroid Eye Disease.","authors":"Mingsu Shi, Rongmei Zhou, Weiai Shen, Yu Liang, Yihan Zhang, Lingyun Liu, Runyi Shao, Yanxi Fang, Chen Zhao, Lianqun Wu","doi":"10.1167/iovs.66.3.46","DOIUrl":null,"url":null,"abstract":"Purpose: Thyroid eye disease (TED) is a visually debilitating and cosmetically disfiguring orbital disorder, characterized by the remodeling of extraocular muscles (EOMs). This study aimed to investigate the role of long non-coding RNA (lncRNA) ENST00000581911 in the EOMs of TED.Methods: LncRNA microarray analysis was performed on EOM tissues sampled from patients with TED and patients with concomitant esotropia. LncRNA ENST00000581911 was identified and subjected to bioinformatics analysis. High-throughput RNA sequencing, CCK-8 assay, CFSE staining, and ELISA were used to investigate the regulatory function of ENST00000581911 in vitro. Furthermore, RNA pull-down, liquid chromatography-tandem mass spectrometry (LC-MS/MS), and western blot (WB) analyses were applied to identify the RNA-binding protein (RBP) interacting with ENST00000581911.Results: A total of 1261 lncRNAs were found to be differentially expressed in the EOMs of TED, with 648 upregulated and 613 downregulated lncRNAs. Among these, the upregulated lncRNA ENST00000581911 exhibited the highest expression level, as validated by quantitative real-time PCR (qRT-PCR). Functional analysis demonstrated that ENST00000581911 might be involved in inflammatory response, regulation of muscle contraction, and amino sugar and nucleotide sugar metabolism. RNA sequencing of ENST00000581911-overexpressing and control orbital fibroblasts (OFs) showed that ENST00000581911 might play a regulatory role in DNA replication, extracellular matrix, and cell cycle. Furthermore, KHSRP was identified as the RBP of ENST00000581911. Overexpression of ENST00000581911 promoted cell proliferation and hyaluronic acid secretion in OFs, whereas silencing KHSRP attenuated these effects.Conclusions: This study provides novel insights into the role of lncRNA ENST00000581911 in the pathogenesis of EOM remodeling in TED. ENST00000581911 may serve as a potential therapeutic target of TED.","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"46"},"PeriodicalIF":5.0000,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11935560/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Investigative ophthalmology & visual science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1167/iovs.66.3.46","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: Thyroid eye disease (TED) is a visually debilitating and cosmetically disfiguring orbital disorder, characterized by the remodeling of extraocular muscles (EOMs). This study aimed to investigate the role of long non-coding RNA (lncRNA) ENST00000581911 in the EOMs of TED.

Methods: LncRNA microarray analysis was performed on EOM tissues sampled from patients with TED and patients with concomitant esotropia. LncRNA ENST00000581911 was identified and subjected to bioinformatics analysis. High-throughput RNA sequencing, CCK-8 assay, CFSE staining, and ELISA were used to investigate the regulatory function of ENST00000581911 in vitro. Furthermore, RNA pull-down, liquid chromatography-tandem mass spectrometry (LC-MS/MS), and western blot (WB) analyses were applied to identify the RNA-binding protein (RBP) interacting with ENST00000581911.

Results: A total of 1261 lncRNAs were found to be differentially expressed in the EOMs of TED, with 648 upregulated and 613 downregulated lncRNAs. Among these, the upregulated lncRNA ENST00000581911 exhibited the highest expression level, as validated by quantitative real-time PCR (qRT-PCR). Functional analysis demonstrated that ENST00000581911 might be involved in inflammatory response, regulation of muscle contraction, and amino sugar and nucleotide sugar metabolism. RNA sequencing of ENST00000581911-overexpressing and control orbital fibroblasts (OFs) showed that ENST00000581911 might play a regulatory role in DNA replication, extracellular matrix, and cell cycle. Furthermore, KHSRP was identified as the RBP of ENST00000581911. Overexpression of ENST00000581911 promoted cell proliferation and hyaluronic acid secretion in OFs, whereas silencing KHSRP attenuated these effects.

Conclusions: This study provides novel insights into the role of lncRNA ENST00000581911 in the pathogenesis of EOM remodeling in TED. ENST00000581911 may serve as a potential therapeutic target of TED.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Investigative ophthalmology & visual science 医学-眼科学

CiteScore

6.90

自引率

4.50%

发文量

339

审稿时长

1 months

期刊介绍： Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.