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A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection

BACKGROUND: Bone formation and loss are the characteristic clinical manifestations of leprosy, but the mechanisms underlying the bone remodeling with Mycobacterium leprae (M. leprae) infection are unclear. METHODOLOGY/PRINCIPAL FINDINGS: Osteocytes may have a role through regulating the differentiat...

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Autores principales: Gao, Zheng-Rong, Liu, Qiong, Zhao, Jie, Zhao, Ya-Qiong, Tan, Li, Zhang, Shao-Hui, Zhou, Ying-Hui, Chen, Yun, Guo, Yue, Feng, Yun-Zhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098081/
https://www.ncbi.nlm.nih.gov/pubmed/35500036
http://dx.doi.org/10.1371/journal.pntd.0010379
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author Gao, Zheng-Rong
Liu, Qiong
Zhao, Jie
Zhao, Ya-Qiong
Tan, Li
Zhang, Shao-Hui
Zhou, Ying-Hui
Chen, Yun
Guo, Yue
Feng, Yun-Zhi
author_facet Gao, Zheng-Rong
Liu, Qiong
Zhao, Jie
Zhao, Ya-Qiong
Tan, Li
Zhang, Shao-Hui
Zhou, Ying-Hui
Chen, Yun
Guo, Yue
Feng, Yun-Zhi
author_sort Gao, Zheng-Rong
collection PubMed
description BACKGROUND: Bone formation and loss are the characteristic clinical manifestations of leprosy, but the mechanisms underlying the bone remodeling with Mycobacterium leprae (M. leprae) infection are unclear. METHODOLOGY/PRINCIPAL FINDINGS: Osteocytes may have a role through regulating the differentiation of osteogenic lineages. To investigate osteocyte-related mechanisms in leprosy, we treated osteocyte-like cell with N-glycosylated muramyl dipeptide (N.g MDP). RNA-seq analysis showed 724 differentially expressed messenger RNAs (mRNAs) and 724 differentially expressed circular RNA (circRNAs). Of these, we filtered through eight osteogenic-related differentially expressed genes, according to the characteristic of competing endogenous RNA, PubMed databases, and bioinformatic analysis, including TargetScan, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. Based on these results, we built a circRNA–microRNA (miRNA)–mRNA triple network. Quantitative reverse-transcription polymerase chain reaction and western blots analyses confirmed decreased Clock expression in osteocyte-like cell, while increased in bone mesenchymal stem cells (BMSCs), implicating a crucial factor in osteogenic differentiation. Immunohistochemistry showed obviously increased expression of CLOCK protein in BMSCs and osteoblasts in N.g MDP–treated mice, but decreased expression in osteocytes. CONCLUSIONS/SIGNIFICANCE: This analytical method provided a basis for the relationship between N.g MDP and remodeling in osteocytes, and the circRNA–miRNA–mRNA triple network may offer a new target for leprosy therapeutics.
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spelling pubmed-90980812022-05-13 A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection Gao, Zheng-Rong Liu, Qiong Zhao, Jie Zhao, Ya-Qiong Tan, Li Zhang, Shao-Hui Zhou, Ying-Hui Chen, Yun Guo, Yue Feng, Yun-Zhi PLoS Negl Trop Dis Research Article BACKGROUND: Bone formation and loss are the characteristic clinical manifestations of leprosy, but the mechanisms underlying the bone remodeling with Mycobacterium leprae (M. leprae) infection are unclear. METHODOLOGY/PRINCIPAL FINDINGS: Osteocytes may have a role through regulating the differentiation of osteogenic lineages. To investigate osteocyte-related mechanisms in leprosy, we treated osteocyte-like cell with N-glycosylated muramyl dipeptide (N.g MDP). RNA-seq analysis showed 724 differentially expressed messenger RNAs (mRNAs) and 724 differentially expressed circular RNA (circRNAs). Of these, we filtered through eight osteogenic-related differentially expressed genes, according to the characteristic of competing endogenous RNA, PubMed databases, and bioinformatic analysis, including TargetScan, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. Based on these results, we built a circRNA–microRNA (miRNA)–mRNA triple network. Quantitative reverse-transcription polymerase chain reaction and western blots analyses confirmed decreased Clock expression in osteocyte-like cell, while increased in bone mesenchymal stem cells (BMSCs), implicating a crucial factor in osteogenic differentiation. Immunohistochemistry showed obviously increased expression of CLOCK protein in BMSCs and osteoblasts in N.g MDP–treated mice, but decreased expression in osteocytes. CONCLUSIONS/SIGNIFICANCE: This analytical method provided a basis for the relationship between N.g MDP and remodeling in osteocytes, and the circRNA–miRNA–mRNA triple network may offer a new target for leprosy therapeutics. Public Library of Science 2022-05-02 /pmc/articles/PMC9098081/ /pubmed/35500036 http://dx.doi.org/10.1371/journal.pntd.0010379 Text en © 2022 Gao et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Gao, Zheng-Rong
Liu, Qiong
Zhao, Jie
Zhao, Ya-Qiong
Tan, Li
Zhang, Shao-Hui
Zhou, Ying-Hui
Chen, Yun
Guo, Yue
Feng, Yun-Zhi
A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection
title A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection
title_full A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection
title_fullStr A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection
title_full_unstemmed A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection
title_short A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection
title_sort comprehensive analysis of the circrna–mirna–mrna network in osteocyte-like cell associated with mycobacterium leprae infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098081/
https://www.ncbi.nlm.nih.gov/pubmed/35500036
http://dx.doi.org/10.1371/journal.pntd.0010379
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