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RNAa-mediated epigenetic attenuation of the cell senescence via locus specific induction of endogenous SIRT1

SIRT1, a known regulator of cellular senescence, is a therapeutic target for age related disorders and its upregulation is a strategy to improve the cell therapeutic potentials of human mesenchymal stem cell (MSCs). Knockdown of natural antisense transcripts via small activating RNAs (RNAa) is an em...

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Autores principales: Mokhberian, Neda, Sharifi, Kazem, Soleymaninejadian, Ehsan, Eftekhary, Mohamad, Hashemi, Seyed Mahmoud, Farhadi, Shohreh, Miwa, Satomi, Ghanbarian, Hossein
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500079/
https://www.ncbi.nlm.nih.gov/pubmed/36138054
http://dx.doi.org/10.1038/s41598-022-17972-9
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author Mokhberian, Neda
Sharifi, Kazem
Soleymaninejadian, Ehsan
Eftekhary, Mohamad
Hashemi, Seyed Mahmoud
Farhadi, Shohreh
Miwa, Satomi
Ghanbarian, Hossein
author_facet Mokhberian, Neda
Sharifi, Kazem
Soleymaninejadian, Ehsan
Eftekhary, Mohamad
Hashemi, Seyed Mahmoud
Farhadi, Shohreh
Miwa, Satomi
Ghanbarian, Hossein
author_sort Mokhberian, Neda
collection PubMed
description SIRT1, a known regulator of cellular senescence, is a therapeutic target for age related disorders and its upregulation is a strategy to improve the cell therapeutic potentials of human mesenchymal stem cell (MSCs). Knockdown of natural antisense transcripts via small activating RNAs (RNAa) is an emerging approach for safe and locus specific gene regulation. We have recently identified a natural antisense transcript at human SIRT1 locus (SIRT1-NAT), the expression of which shows a negative correlation with that of SIRT1. To test the hypothetic upregulation of SIRT1 via knockdown of SIRT1-NAT, in this study we designed a single stranded oligonucleotide (SIRT1-antagoNAT) against the antisense transcript, transfection of which efficiently knocked down the SIRT1-NAT and induced SIRT1 transcription in human MSCs. In addition, activation of SIRT1 transfection via knockdown of SIRT1-NAT in human MSCs enhanced their proliferation and differentiation potentials, reduced senescence associated β-galactosidase activity and reversed the senescence associated molecular alterations. Our findings introduce an RNAa mediated approach for epigenetic induction of endogenous SIRT1 and the consequent attenuation of senescence. Further studies should evaluate the therapeutic potentials of this approach against various age related disorders.
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spelling pubmed-95000792022-09-24 RNAa-mediated epigenetic attenuation of the cell senescence via locus specific induction of endogenous SIRT1 Mokhberian, Neda Sharifi, Kazem Soleymaninejadian, Ehsan Eftekhary, Mohamad Hashemi, Seyed Mahmoud Farhadi, Shohreh Miwa, Satomi Ghanbarian, Hossein Sci Rep Article SIRT1, a known regulator of cellular senescence, is a therapeutic target for age related disorders and its upregulation is a strategy to improve the cell therapeutic potentials of human mesenchymal stem cell (MSCs). Knockdown of natural antisense transcripts via small activating RNAs (RNAa) is an emerging approach for safe and locus specific gene regulation. We have recently identified a natural antisense transcript at human SIRT1 locus (SIRT1-NAT), the expression of which shows a negative correlation with that of SIRT1. To test the hypothetic upregulation of SIRT1 via knockdown of SIRT1-NAT, in this study we designed a single stranded oligonucleotide (SIRT1-antagoNAT) against the antisense transcript, transfection of which efficiently knocked down the SIRT1-NAT and induced SIRT1 transcription in human MSCs. In addition, activation of SIRT1 transfection via knockdown of SIRT1-NAT in human MSCs enhanced their proliferation and differentiation potentials, reduced senescence associated β-galactosidase activity and reversed the senescence associated molecular alterations. Our findings introduce an RNAa mediated approach for epigenetic induction of endogenous SIRT1 and the consequent attenuation of senescence. Further studies should evaluate the therapeutic potentials of this approach against various age related disorders. Nature Publishing Group UK 2022-09-22 /pmc/articles/PMC9500079/ /pubmed/36138054 http://dx.doi.org/10.1038/s41598-022-17972-9 Text en © The Author(s) 2022, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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/) .
spellingShingle Article
Mokhberian, Neda
Sharifi, Kazem
Soleymaninejadian, Ehsan
Eftekhary, Mohamad
Hashemi, Seyed Mahmoud
Farhadi, Shohreh
Miwa, Satomi
Ghanbarian, Hossein
RNAa-mediated epigenetic attenuation of the cell senescence via locus specific induction of endogenous SIRT1
title RNAa-mediated epigenetic attenuation of the cell senescence via locus specific induction of endogenous SIRT1
title_full RNAa-mediated epigenetic attenuation of the cell senescence via locus specific induction of endogenous SIRT1
title_fullStr RNAa-mediated epigenetic attenuation of the cell senescence via locus specific induction of endogenous SIRT1
title_full_unstemmed RNAa-mediated epigenetic attenuation of the cell senescence via locus specific induction of endogenous SIRT1
title_short RNAa-mediated epigenetic attenuation of the cell senescence via locus specific induction of endogenous SIRT1
title_sort rnaa-mediated epigenetic attenuation of the cell senescence via locus specific induction of endogenous sirt1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500079/
https://www.ncbi.nlm.nih.gov/pubmed/36138054
http://dx.doi.org/10.1038/s41598-022-17972-9
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