The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients

BACKGROUND: Mesenchymal stem cells including adipose-derived stem cells (ASCs) have a considerable potential in the field of translational medicine. Unfortunately, multiple factors (e.g., older age, co-existing diabetes, and obesity) may impair cellular function, which hinders the overall effectiven...

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Autores principales: Ren, Sen, Xiong, Hewei, Chen, Jing, Yang, Xiaofan, Liu, Yutian, Guo, Jiahe, Jiang, Tao, Xu, Zhao, Yuan, Meng, Liu, Yang, Zhou, Nan, Chen, Hongrui, Li, Wenqing, Machens, Hans-Günther, Chen, Zhenbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164820/
https://www.ncbi.nlm.nih.gov/pubmed/34051854
http://dx.doi.org/10.1186/s13287-021-02388-5
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author Ren, Sen
Xiong, Hewei
Chen, Jing
Yang, Xiaofan
Liu, Yutian
Guo, Jiahe
Jiang, Tao
Xu, Zhao
Yuan, Meng
Liu, Yang
Zhou, Nan
Chen, Hongrui
Li, Wenqing
Machens, Hans-Günther
Chen, Zhenbing
author_facet Ren, Sen
Xiong, Hewei
Chen, Jing
Yang, Xiaofan
Liu, Yutian
Guo, Jiahe
Jiang, Tao
Xu, Zhao
Yuan, Meng
Liu, Yang
Zhou, Nan
Chen, Hongrui
Li, Wenqing
Machens, Hans-Günther
Chen, Zhenbing
author_sort Ren, Sen
collection PubMed
description BACKGROUND: Mesenchymal stem cells including adipose-derived stem cells (ASCs) have a considerable potential in the field of translational medicine. Unfortunately, multiple factors (e.g., older age, co-existing diabetes, and obesity) may impair cellular function, which hinders the overall effectiveness of autologous stem cell therapy. Noncoding RNAs—including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs)—have been shown to play important roles in stem cell biology. However, the overall diabetes-related and aging-related expression patterns and interactions of these RNAs in ASCs remain unknown. METHOD: The phenotypes and functions of ASCs isolated from diabetic (D-ASCs), old (O-ASCs), and young (Y-ASCs) donors were evaluated by in vitro assays. We conducted high-throughput RNA sequencing (RNA-seq) in these ASCs to identify the differentially expressed (DE) RNAs. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analyses were performed to investigate mRNAs with significant differences among groups. The lncRNA- or circRNA-associated competing endogenous RNA (ceRNA) networks were constructed based on bioinformatics analyses and real-time polymerase chain reaction (RT-PCR) results. The miR-145-5p mimics were transfected into O-ASCs and verified by PCR. RESULTS: ASCs from diabetic and old donors showed inferior migration ability and increased cellular senescence. Furthermore, O-ASCs have decreased capacities for promoting endothelial cell angiogenesis and fibroblast migration, compared with Y-ASCs. The DE miRNAs, mRNAs, lncRNAs, and circRNAs were successfully identified by RNA-seq in O-ASCs vs. Y-ASCs and D-ASCs vs. O-ASCs. GO and KEGG analyses demonstrated that DE mRNAs were significantly enriched in aging and cell senescence terms separately. PPI networks revealed critical DE mRNAs in the above groups. RNAs with high fold changes and low p values were validated by PCR. ceRNA networks were constructed based on bioinformatics analyses and validated RNAs. Additionally, the lncRNA RAET1E-AS1–miR-145-5p–WNT11/BMPER axis was validated by PCR and correlation analyses. Finally, the overexpression of miR-145-5p was found to rejuvenate O-ASCs phenotype and augment the functionality of these cells. CONCLUSION: Our research may provide insights regarding the underlying mechanisms of ASC dysfunction; it may also offer novel targets for restoring therapeutic properties in ASCs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02388-5.
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spelling pubmed-81648202021-06-01 The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients Ren, Sen Xiong, Hewei Chen, Jing Yang, Xiaofan Liu, Yutian Guo, Jiahe Jiang, Tao Xu, Zhao Yuan, Meng Liu, Yang Zhou, Nan Chen, Hongrui Li, Wenqing Machens, Hans-Günther Chen, Zhenbing Stem Cell Res Ther Research BACKGROUND: Mesenchymal stem cells including adipose-derived stem cells (ASCs) have a considerable potential in the field of translational medicine. Unfortunately, multiple factors (e.g., older age, co-existing diabetes, and obesity) may impair cellular function, which hinders the overall effectiveness of autologous stem cell therapy. Noncoding RNAs—including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs)—have been shown to play important roles in stem cell biology. However, the overall diabetes-related and aging-related expression patterns and interactions of these RNAs in ASCs remain unknown. METHOD: The phenotypes and functions of ASCs isolated from diabetic (D-ASCs), old (O-ASCs), and young (Y-ASCs) donors were evaluated by in vitro assays. We conducted high-throughput RNA sequencing (RNA-seq) in these ASCs to identify the differentially expressed (DE) RNAs. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analyses were performed to investigate mRNAs with significant differences among groups. The lncRNA- or circRNA-associated competing endogenous RNA (ceRNA) networks were constructed based on bioinformatics analyses and real-time polymerase chain reaction (RT-PCR) results. The miR-145-5p mimics were transfected into O-ASCs and verified by PCR. RESULTS: ASCs from diabetic and old donors showed inferior migration ability and increased cellular senescence. Furthermore, O-ASCs have decreased capacities for promoting endothelial cell angiogenesis and fibroblast migration, compared with Y-ASCs. The DE miRNAs, mRNAs, lncRNAs, and circRNAs were successfully identified by RNA-seq in O-ASCs vs. Y-ASCs and D-ASCs vs. O-ASCs. GO and KEGG analyses demonstrated that DE mRNAs were significantly enriched in aging and cell senescence terms separately. PPI networks revealed critical DE mRNAs in the above groups. RNAs with high fold changes and low p values were validated by PCR. ceRNA networks were constructed based on bioinformatics analyses and validated RNAs. Additionally, the lncRNA RAET1E-AS1–miR-145-5p–WNT11/BMPER axis was validated by PCR and correlation analyses. Finally, the overexpression of miR-145-5p was found to rejuvenate O-ASCs phenotype and augment the functionality of these cells. CONCLUSION: Our research may provide insights regarding the underlying mechanisms of ASC dysfunction; it may also offer novel targets for restoring therapeutic properties in ASCs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02388-5. BioMed Central 2021-05-29 /pmc/articles/PMC8164820/ /pubmed/34051854 http://dx.doi.org/10.1186/s13287-021-02388-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ren, Sen
Xiong, Hewei
Chen, Jing
Yang, Xiaofan
Liu, Yutian
Guo, Jiahe
Jiang, Tao
Xu, Zhao
Yuan, Meng
Liu, Yang
Zhou, Nan
Chen, Hongrui
Li, Wenqing
Machens, Hans-Günther
Chen, Zhenbing
The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients
title The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients
title_full The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients
title_fullStr The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients
title_full_unstemmed The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients
title_short The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients
title_sort whole profiling and competing endogenous rna network analyses of noncoding rnas in adipose-derived stem cells from diabetic, old, and young patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164820/
https://www.ncbi.nlm.nih.gov/pubmed/34051854
http://dx.doi.org/10.1186/s13287-021-02388-5
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