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Aberrant lncRNA–mRNA expression profile and function networks during the adipogenesis of mesenchymal stem cells from patients with ankylosing spondylitis
Objective: We have already demonstrated that mesenchymal stem cells from patients with ankylosing spondylitis (ASMSCs) exhibited greater adipogenic differentiation potential than those from healthy donors (HDMSCs). Here, we further investigated the expression profile of long noncoding RNA (lncRNA) a...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9563993/ https://www.ncbi.nlm.nih.gov/pubmed/36246583 http://dx.doi.org/10.3389/fgene.2022.991875 |
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author | Cen, Shuizhong Cai, Mingxi Wang, Yihan Lu, Xiuyi Chen, Zhipeng Chen, Haobo Fang, Yingdong Wu, Changping Qiu, Sujun Liu, Zhenhua |
author_facet | Cen, Shuizhong Cai, Mingxi Wang, Yihan Lu, Xiuyi Chen, Zhipeng Chen, Haobo Fang, Yingdong Wu, Changping Qiu, Sujun Liu, Zhenhua |
author_sort | Cen, Shuizhong |
collection | PubMed |
description | Objective: We have already demonstrated that mesenchymal stem cells from patients with ankylosing spondylitis (ASMSCs) exhibited greater adipogenic differentiation potential than those from healthy donors (HDMSCs). Here, we further investigated the expression profile of long noncoding RNA (lncRNA) and mRNA, aiming to explore the underlying mechanism of abnormal adipogenic differentiation in ASMSCs. Methods: HDMSCs and ASMSCs were separately isolated and induced with adipogenic differentiation medium for 10 days. Thereafter, lncRNAs and mRNAs that were differentially expressed (DE) between HDMSCs and ASMSCs were identified via high-throughput sequencing and confirmed by quantitative real-time PCR (qRT–PCR) assays. Then, the DE genes were annotated and enriched by GO analysis. In addition, protein interaction network was constructed to evaluate the interactions between DE mRNAs and to find hub nodes and study cliques. Besides, co-expression network analysis was carried out to assess the co-expressions between DE mRNA and DE lncRNAs, and competing endogenous RNA (ceRNA) network analysis were conducted to predict the relationships among lncRNAs, mRNAs and miRNAs. The signaling pathways based on the DE genes and the predicted DE genes were enriched by KEGG analysis. Results: A total of 263 DE lncRNAs and 1376 DE mRNAs were found during adipogenesis in ASMSCs. qRT–PCR indicated that the expression of the top 20 mRNAs and the top 10 lncRNAs was consistent with the high-throughput sequencing data. Several lncRNAs (NR_125386.1, NR_046473.1 and NR_038937.1) and their target genes (SPN and OR1AIP2), together with the significantly co-expressed pairs of DE lncRNAs and DE mRNAs (SLC38A5-ENST00000429588.1, TMEM61-ENST00000400755.3 and C5orf46-ENST00000512300.1), were closely related to the enhanced adipogenesis of ASMSCs by modulating the PPAR signaling pathway. Conclusion: Our study analyzed the expression profiles of DE lncRNAs and DE mRNAs during adipogenesis in ASMSCs and HDMSCs. Several DE lncRNAs, DE mRNAs and signaling pathways that probably participate in the aberrant adipogenesis of ASMSCs were selected for future study. These results will likely provide potential targets for our intervention on fat metaplasia and subsequent new bone formation in patients with AS in the future. |
format | Online Article Text |
id | pubmed-9563993 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95639932022-10-15 Aberrant lncRNA–mRNA expression profile and function networks during the adipogenesis of mesenchymal stem cells from patients with ankylosing spondylitis Cen, Shuizhong Cai, Mingxi Wang, Yihan Lu, Xiuyi Chen, Zhipeng Chen, Haobo Fang, Yingdong Wu, Changping Qiu, Sujun Liu, Zhenhua Front Genet Genetics Objective: We have already demonstrated that mesenchymal stem cells from patients with ankylosing spondylitis (ASMSCs) exhibited greater adipogenic differentiation potential than those from healthy donors (HDMSCs). Here, we further investigated the expression profile of long noncoding RNA (lncRNA) and mRNA, aiming to explore the underlying mechanism of abnormal adipogenic differentiation in ASMSCs. Methods: HDMSCs and ASMSCs were separately isolated and induced with adipogenic differentiation medium for 10 days. Thereafter, lncRNAs and mRNAs that were differentially expressed (DE) between HDMSCs and ASMSCs were identified via high-throughput sequencing and confirmed by quantitative real-time PCR (qRT–PCR) assays. Then, the DE genes were annotated and enriched by GO analysis. In addition, protein interaction network was constructed to evaluate the interactions between DE mRNAs and to find hub nodes and study cliques. Besides, co-expression network analysis was carried out to assess the co-expressions between DE mRNA and DE lncRNAs, and competing endogenous RNA (ceRNA) network analysis were conducted to predict the relationships among lncRNAs, mRNAs and miRNAs. The signaling pathways based on the DE genes and the predicted DE genes were enriched by KEGG analysis. Results: A total of 263 DE lncRNAs and 1376 DE mRNAs were found during adipogenesis in ASMSCs. qRT–PCR indicated that the expression of the top 20 mRNAs and the top 10 lncRNAs was consistent with the high-throughput sequencing data. Several lncRNAs (NR_125386.1, NR_046473.1 and NR_038937.1) and their target genes (SPN and OR1AIP2), together with the significantly co-expressed pairs of DE lncRNAs and DE mRNAs (SLC38A5-ENST00000429588.1, TMEM61-ENST00000400755.3 and C5orf46-ENST00000512300.1), were closely related to the enhanced adipogenesis of ASMSCs by modulating the PPAR signaling pathway. Conclusion: Our study analyzed the expression profiles of DE lncRNAs and DE mRNAs during adipogenesis in ASMSCs and HDMSCs. Several DE lncRNAs, DE mRNAs and signaling pathways that probably participate in the aberrant adipogenesis of ASMSCs were selected for future study. These results will likely provide potential targets for our intervention on fat metaplasia and subsequent new bone formation in patients with AS in the future. Frontiers Media S.A. 2022-10-03 /pmc/articles/PMC9563993/ /pubmed/36246583 http://dx.doi.org/10.3389/fgene.2022.991875 Text en Copyright © 2022 Cen, Cai, Wang, Lu, Chen, Chen, Fang, Wu, Qiu and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Cen, Shuizhong Cai, Mingxi Wang, Yihan Lu, Xiuyi Chen, Zhipeng Chen, Haobo Fang, Yingdong Wu, Changping Qiu, Sujun Liu, Zhenhua Aberrant lncRNA–mRNA expression profile and function networks during the adipogenesis of mesenchymal stem cells from patients with ankylosing spondylitis |
title | Aberrant lncRNA–mRNA expression profile and function networks during the adipogenesis of mesenchymal stem cells from patients with ankylosing spondylitis |
title_full | Aberrant lncRNA–mRNA expression profile and function networks during the adipogenesis of mesenchymal stem cells from patients with ankylosing spondylitis |
title_fullStr | Aberrant lncRNA–mRNA expression profile and function networks during the adipogenesis of mesenchymal stem cells from patients with ankylosing spondylitis |
title_full_unstemmed | Aberrant lncRNA–mRNA expression profile and function networks during the adipogenesis of mesenchymal stem cells from patients with ankylosing spondylitis |
title_short | Aberrant lncRNA–mRNA expression profile and function networks during the adipogenesis of mesenchymal stem cells from patients with ankylosing spondylitis |
title_sort | aberrant lncrna–mrna expression profile and function networks during the adipogenesis of mesenchymal stem cells from patients with ankylosing spondylitis |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9563993/ https://www.ncbi.nlm.nih.gov/pubmed/36246583 http://dx.doi.org/10.3389/fgene.2022.991875 |
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