Identification of the regulatory role of lncRNA HCG18 in myasthenia gravis by integrated bioinformatics and experimental analyses

Abstract Background Long non-coding RNAs (lncRNAs), functioning as competing endogenous RNAs (ceRNAs), have been reported to play important roles in the pathogenesis of autoimmune diseases. However, little is known about the regulatory roles of lncRNAs underlying the mechanism of myasthenia gravis (...

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Autores principales:	Shuang Li, Xu Wang, Tianfeng Wang, Huixue Zhang, Xiaoyu Lu, Li Liu, Lifang Li, Chunrui Bo, Xiaotong Kong, Si Xu, Shangwei Ning, Jianjian Wang, Lihua Wang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Myasthenia gravis HCG18 miR-145-5p CD28 Network analysis Random walk with restart Medicine R
Acceso en línea:	https://doaj.org/article/4e711648554f409c997f66e300bcd0f5
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spelling	oai:doaj.org-article:4e711648554f409c997f66e300bcd0f52021-11-21T12:05:03ZIdentification of the regulatory role of lncRNA HCG18 in myasthenia gravis by integrated bioinformatics and experimental analyses10.1186/s12967-021-03138-01479-5876https://doaj.org/article/4e711648554f409c997f66e300bcd0f52021-11-01T00:00:00Zhttps://doi.org/10.1186/s12967-021-03138-0https://doaj.org/toc/1479-5876Abstract Background Long non-coding RNAs (lncRNAs), functioning as competing endogenous RNAs (ceRNAs), have been reported to play important roles in the pathogenesis of autoimmune diseases. However, little is known about the regulatory roles of lncRNAs underlying the mechanism of myasthenia gravis (MG). The aim of the present study was to explore the roles of lncRNAs as ceRNAs associated with the progression of MG. Methods MG risk genes and miRNAs were obtained from public databases. Protein–protein interaction (PPI) network analysis and module analysis were performed. A lncRNA-mediated module-associated ceRNA (LMMAC) network, which integrated risk genes in modules, risk miRNAs and predicted lncRNAs, was constructed to systematically explore the regulatory roles of lncRNAs in MG. Through performing random walk with restart on the network, HCG18/miR-145-5p/CD28 ceRNA axis was found to play important roles in MG, potentially. The expression of HCG18 in MG patients was detected using RT-PCR. The effects of HCG18 knockdown on cell proliferation and apoptosis were determined by CCK-8 assay and flow cytometry. The interactions among HCG18, miR-145-5p and CD28 were explored by luciferase assay, RT-PCR and western blot assay. Results Based on PPI network, we identified 9 modules. Functional enrichment analyses revealed these modules were enriched in immune-related signaling pathways. We then constructed LMMAC network, containing 25 genes, 50 miRNAs, and 64 lncRNAs. Through bioinformatics algorithm, we found lncRNA HCG18 as a ceRNA, might play important roles in MG. Further experiments indicated that HCG18 was overexpressed in MG patients and was a target of miR-145-5p. Functional assays illustrated that HCG18 suppressed Jurkat cell apoptosis and promoted cell proliferation. Mechanistically, knockdown of HCG18 inhibited the CD28 mRNA and protein expression levels in Jurkat cells, while miR-145-5p inhibitor blocked the reduction of CD28 expression induced by HCG18 suppression. Conclusion We have reported a novel HCG18/miR-145-5p/CD28 ceRNA axis in MG. Our findings will contribute to a deeper understanding of the molecular mechanism of and provide a novel potential therapeutic target for MG.Shuang LiXu WangTianfeng WangHuixue ZhangXiaoyu LuLi LiuLifang LiChunrui BoXiaotong KongSi XuShangwei NingJianjian WangLihua WangBMCarticleMyasthenia gravisHCG18miR-145-5pCD28Network analysisRandom walk with restartMedicineRENJournal of Translational Medicine, Vol 19, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Myasthenia gravis HCG18 miR-145-5p CD28 Network analysis Random walk with restart Medicine R
spellingShingle	Myasthenia gravis HCG18 miR-145-5p CD28 Network analysis Random walk with restart Medicine R Shuang Li Xu Wang Tianfeng Wang Huixue Zhang Xiaoyu Lu Li Liu Lifang Li Chunrui Bo Xiaotong Kong Si Xu Shangwei Ning Jianjian Wang Lihua Wang Identification of the regulatory role of lncRNA HCG18 in myasthenia gravis by integrated bioinformatics and experimental analyses
description	Abstract Background Long non-coding RNAs (lncRNAs), functioning as competing endogenous RNAs (ceRNAs), have been reported to play important roles in the pathogenesis of autoimmune diseases. However, little is known about the regulatory roles of lncRNAs underlying the mechanism of myasthenia gravis (MG). The aim of the present study was to explore the roles of lncRNAs as ceRNAs associated with the progression of MG. Methods MG risk genes and miRNAs were obtained from public databases. Protein–protein interaction (PPI) network analysis and module analysis were performed. A lncRNA-mediated module-associated ceRNA (LMMAC) network, which integrated risk genes in modules, risk miRNAs and predicted lncRNAs, was constructed to systematically explore the regulatory roles of lncRNAs in MG. Through performing random walk with restart on the network, HCG18/miR-145-5p/CD28 ceRNA axis was found to play important roles in MG, potentially. The expression of HCG18 in MG patients was detected using RT-PCR. The effects of HCG18 knockdown on cell proliferation and apoptosis were determined by CCK-8 assay and flow cytometry. The interactions among HCG18, miR-145-5p and CD28 were explored by luciferase assay, RT-PCR and western blot assay. Results Based on PPI network, we identified 9 modules. Functional enrichment analyses revealed these modules were enriched in immune-related signaling pathways. We then constructed LMMAC network, containing 25 genes, 50 miRNAs, and 64 lncRNAs. Through bioinformatics algorithm, we found lncRNA HCG18 as a ceRNA, might play important roles in MG. Further experiments indicated that HCG18 was overexpressed in MG patients and was a target of miR-145-5p. Functional assays illustrated that HCG18 suppressed Jurkat cell apoptosis and promoted cell proliferation. Mechanistically, knockdown of HCG18 inhibited the CD28 mRNA and protein expression levels in Jurkat cells, while miR-145-5p inhibitor blocked the reduction of CD28 expression induced by HCG18 suppression. Conclusion We have reported a novel HCG18/miR-145-5p/CD28 ceRNA axis in MG. Our findings will contribute to a deeper understanding of the molecular mechanism of and provide a novel potential therapeutic target for MG.
format	article
author	Shuang Li Xu Wang Tianfeng Wang Huixue Zhang Xiaoyu Lu Li Liu Lifang Li Chunrui Bo Xiaotong Kong Si Xu Shangwei Ning Jianjian Wang Lihua Wang
author_facet	Shuang Li Xu Wang Tianfeng Wang Huixue Zhang Xiaoyu Lu Li Liu Lifang Li Chunrui Bo Xiaotong Kong Si Xu Shangwei Ning Jianjian Wang Lihua Wang
author_sort	Shuang Li
title	Identification of the regulatory role of lncRNA HCG18 in myasthenia gravis by integrated bioinformatics and experimental analyses
title_short	Identification of the regulatory role of lncRNA HCG18 in myasthenia gravis by integrated bioinformatics and experimental analyses
title_full	Identification of the regulatory role of lncRNA HCG18 in myasthenia gravis by integrated bioinformatics and experimental analyses
title_fullStr	Identification of the regulatory role of lncRNA HCG18 in myasthenia gravis by integrated bioinformatics and experimental analyses
title_full_unstemmed	Identification of the regulatory role of lncRNA HCG18 in myasthenia gravis by integrated bioinformatics and experimental analyses
title_sort	identification of the regulatory role of lncrna hcg18 in myasthenia gravis by integrated bioinformatics and experimental analyses
publisher	BMC
publishDate	2021
url	https://doaj.org/article/4e711648554f409c997f66e300bcd0f5
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Identification of the regulatory role of lncRNA HCG18 in myasthenia gravis by integrated bioinformatics and experimental analyses

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