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RUNX3 mediates keloid fibroblast proliferation through deacetylation of EZH2 by SIRT1
BACKGROUND: Keloid is a benign proliferative fibrous disease featured by excessive fibroblast proliferation after skin injury. However, the mechanism of abnormal cell proliferation is still unclear. Herein, we investigated the mechanism of abnormal proliferation in keloids involving Sirtuin 1(SIRT1)...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730640/ https://www.ncbi.nlm.nih.gov/pubmed/36476345 http://dx.doi.org/10.1186/s12860-022-00451-4 |
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author | Liu, Hanye Yan, Guanghai Li, Li Wang, Dandan Wang, Yu Jin, Shan Jin, Zhehu Li, Liangchang Zhu, Lianhua |
author_facet | Liu, Hanye Yan, Guanghai Li, Li Wang, Dandan Wang, Yu Jin, Shan Jin, Zhehu Li, Liangchang Zhu, Lianhua |
author_sort | Liu, Hanye |
collection | PubMed |
description | BACKGROUND: Keloid is a benign proliferative fibrous disease featured by excessive fibroblast proliferation after skin injury. However, the mechanism of abnormal cell proliferation is still unclear. Herein, we investigated the mechanism of abnormal proliferation in keloids involving Sirtuin 1(SIRT1)/ Zeste Homolog 2 (EZH2)/ Runt-related transcription factor 3 (RUNX3). METHODS: HE staining was used to observe the histopathological changes. Western blot was performed to detect SIRT1/EZH2/RUNX3 and cell cycle related proteins. RT-PCR detected EZH2 mRNA. After knockdown of EZH2 or overexpression of RUNX3, cell proliferation and cell cycle was analyzed. Immunoprecipitation was used to detect acetylated EZH2. RESULTS: The results showed that overexpression of RUNX3 inhibited cell proliferation and arrested cell cycle at G1/S phase, whereas inhibition of SIRT1 promoted cell proliferation and G1/S phase of the cell cycle. Knockdown of EZH2 promoted the expression of RUNX3, inhibited cell proliferation and shortened the progression of G1 to S phase. Simultaneous knockdown of EZH2 and inhibition of SIRT1 reversed these effects. Inhibition of SIRT1 increased its protein stability by increasing EZH2 acetylation, thereby reducing the expression of RUNX3 and promoting cell proliferation. CONCLUSIONS: Conclusively, the SIRT1/EZH2/RUNX3 axis may be an important pathway in the regulation of abnormal proliferation in keloids. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12860-022-00451-4. |
format | Online Article Text |
id | pubmed-9730640 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-97306402022-12-09 RUNX3 mediates keloid fibroblast proliferation through deacetylation of EZH2 by SIRT1 Liu, Hanye Yan, Guanghai Li, Li Wang, Dandan Wang, Yu Jin, Shan Jin, Zhehu Li, Liangchang Zhu, Lianhua BMC Mol Cell Biol Research BACKGROUND: Keloid is a benign proliferative fibrous disease featured by excessive fibroblast proliferation after skin injury. However, the mechanism of abnormal cell proliferation is still unclear. Herein, we investigated the mechanism of abnormal proliferation in keloids involving Sirtuin 1(SIRT1)/ Zeste Homolog 2 (EZH2)/ Runt-related transcription factor 3 (RUNX3). METHODS: HE staining was used to observe the histopathological changes. Western blot was performed to detect SIRT1/EZH2/RUNX3 and cell cycle related proteins. RT-PCR detected EZH2 mRNA. After knockdown of EZH2 or overexpression of RUNX3, cell proliferation and cell cycle was analyzed. Immunoprecipitation was used to detect acetylated EZH2. RESULTS: The results showed that overexpression of RUNX3 inhibited cell proliferation and arrested cell cycle at G1/S phase, whereas inhibition of SIRT1 promoted cell proliferation and G1/S phase of the cell cycle. Knockdown of EZH2 promoted the expression of RUNX3, inhibited cell proliferation and shortened the progression of G1 to S phase. Simultaneous knockdown of EZH2 and inhibition of SIRT1 reversed these effects. Inhibition of SIRT1 increased its protein stability by increasing EZH2 acetylation, thereby reducing the expression of RUNX3 and promoting cell proliferation. CONCLUSIONS: Conclusively, the SIRT1/EZH2/RUNX3 axis may be an important pathway in the regulation of abnormal proliferation in keloids. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12860-022-00451-4. BioMed Central 2022-12-07 /pmc/articles/PMC9730640/ /pubmed/36476345 http://dx.doi.org/10.1186/s12860-022-00451-4 Text en © The Author(s) 2022 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 Liu, Hanye Yan, Guanghai Li, Li Wang, Dandan Wang, Yu Jin, Shan Jin, Zhehu Li, Liangchang Zhu, Lianhua RUNX3 mediates keloid fibroblast proliferation through deacetylation of EZH2 by SIRT1 |
title | RUNX3 mediates keloid fibroblast proliferation through deacetylation of EZH2 by SIRT1 |
title_full | RUNX3 mediates keloid fibroblast proliferation through deacetylation of EZH2 by SIRT1 |
title_fullStr | RUNX3 mediates keloid fibroblast proliferation through deacetylation of EZH2 by SIRT1 |
title_full_unstemmed | RUNX3 mediates keloid fibroblast proliferation through deacetylation of EZH2 by SIRT1 |
title_short | RUNX3 mediates keloid fibroblast proliferation through deacetylation of EZH2 by SIRT1 |
title_sort | runx3 mediates keloid fibroblast proliferation through deacetylation of ezh2 by sirt1 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730640/ https://www.ncbi.nlm.nih.gov/pubmed/36476345 http://dx.doi.org/10.1186/s12860-022-00451-4 |
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