Cargando…
Hypoxic condition induced H3K27me3 modification of the LncRNA Tmem235 promoter thus supporting apoptosis of BMSCs
Bone marrow mesenchymal stem cells (BMSCs) have strong regenerative potential and show good application prospects for treating clinical diseases. However, in the process of BMSC transplantation for treating ischemic and hypoxic diseases, BMSCs have high rates of apoptosis in the hypoxic microenviron...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482900/ https://www.ncbi.nlm.nih.gov/pubmed/35779185 http://dx.doi.org/10.1007/s10495-022-01747-8 |
_version_ | 1784791554904293376 |
---|---|
author | Zhang, Fei Luo, Hong Peng, Wuxun Wang, Lei Wang, Tao Xie, Zhihong Zhang, Jian Dong, Wentao Zheng, Xiaohan Liu, Gang Zhu, Xuesong Kang, Qinglin Tian, Xiaobin |
author_facet | Zhang, Fei Luo, Hong Peng, Wuxun Wang, Lei Wang, Tao Xie, Zhihong Zhang, Jian Dong, Wentao Zheng, Xiaohan Liu, Gang Zhu, Xuesong Kang, Qinglin Tian, Xiaobin |
author_sort | Zhang, Fei |
collection | PubMed |
description | Bone marrow mesenchymal stem cells (BMSCs) have strong regenerative potential and show good application prospects for treating clinical diseases. However, in the process of BMSC transplantation for treating ischemic and hypoxic diseases, BMSCs have high rates of apoptosis in the hypoxic microenvironment of transplantation, which significantly affects the transplantation efficacy. Our previous studies have confirmed the key role of long non-coding RNA Tmem235 (LncRNA Tmem235) in the process of hypoxia-induced BMSC apoptosis and its downstream regulatory mechanism, but the upstream mechanism by which hypoxia regulates LncRNA Tmem235 expression to induce BMSC apoptosis is still unclear. Under hypoxic conditions, we found that the level of LncRNA Tmem235 promoter histone H3 lysine 27 trimethylation modification (H3K27me3) was significantly increased by CHIP-qPCR. Moreover, H3K27me3 cooperated with LncRNA Tmem235 promoter DNA methylation to inhibit the expression of LncRNA Tmem235 and promote apoptosis of BMSCs. To study the mechanism of hypoxia-induced modification of LncRNA Tmem235 promoter H3K27me3 in the hypoxia model of BMSCs, we detected the expression of H3K27 methylase and histone demethylase and found that only histone methylase enhancer of zeste homolog 2 (EZH2) expression was significantly upregulated. Knockdown of EZH2 significantly decreased the level of H3K27me3 modification in the LncRNA Tmem235 promoter. The EZH2 promoter region contains a hypoxia-responsive element (HRE) that interacts with hypoxia-inducible factor-1alpha (HIF-1α), which is overexpressed under hypoxic conditions, thereby promoting its overexpression. In summary, hypoxia promotes the modification of the LncRNA Tmem235 promoter H3K27me3 through the HIF-1α/EZH2 signaling axis, inhibits the expression of LncRNA Tmem235, and leads to hypoxic apoptosis of BMSCs. Our findings improve the regulatory mechanism of LncRNA Tmem235 during hypoxic apoptosis of BMSCs and provide a more complete theoretical pathway for targeting LncRNA to inhibit hypoxic apoptosis of BMSCs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10495-022-01747-8. |
format | Online Article Text |
id | pubmed-9482900 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-94829002022-09-20 Hypoxic condition induced H3K27me3 modification of the LncRNA Tmem235 promoter thus supporting apoptosis of BMSCs Zhang, Fei Luo, Hong Peng, Wuxun Wang, Lei Wang, Tao Xie, Zhihong Zhang, Jian Dong, Wentao Zheng, Xiaohan Liu, Gang Zhu, Xuesong Kang, Qinglin Tian, Xiaobin Apoptosis Article Bone marrow mesenchymal stem cells (BMSCs) have strong regenerative potential and show good application prospects for treating clinical diseases. However, in the process of BMSC transplantation for treating ischemic and hypoxic diseases, BMSCs have high rates of apoptosis in the hypoxic microenvironment of transplantation, which significantly affects the transplantation efficacy. Our previous studies have confirmed the key role of long non-coding RNA Tmem235 (LncRNA Tmem235) in the process of hypoxia-induced BMSC apoptosis and its downstream regulatory mechanism, but the upstream mechanism by which hypoxia regulates LncRNA Tmem235 expression to induce BMSC apoptosis is still unclear. Under hypoxic conditions, we found that the level of LncRNA Tmem235 promoter histone H3 lysine 27 trimethylation modification (H3K27me3) was significantly increased by CHIP-qPCR. Moreover, H3K27me3 cooperated with LncRNA Tmem235 promoter DNA methylation to inhibit the expression of LncRNA Tmem235 and promote apoptosis of BMSCs. To study the mechanism of hypoxia-induced modification of LncRNA Tmem235 promoter H3K27me3 in the hypoxia model of BMSCs, we detected the expression of H3K27 methylase and histone demethylase and found that only histone methylase enhancer of zeste homolog 2 (EZH2) expression was significantly upregulated. Knockdown of EZH2 significantly decreased the level of H3K27me3 modification in the LncRNA Tmem235 promoter. The EZH2 promoter region contains a hypoxia-responsive element (HRE) that interacts with hypoxia-inducible factor-1alpha (HIF-1α), which is overexpressed under hypoxic conditions, thereby promoting its overexpression. In summary, hypoxia promotes the modification of the LncRNA Tmem235 promoter H3K27me3 through the HIF-1α/EZH2 signaling axis, inhibits the expression of LncRNA Tmem235, and leads to hypoxic apoptosis of BMSCs. Our findings improve the regulatory mechanism of LncRNA Tmem235 during hypoxic apoptosis of BMSCs and provide a more complete theoretical pathway for targeting LncRNA to inhibit hypoxic apoptosis of BMSCs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10495-022-01747-8. Springer US 2022-07-02 2022 /pmc/articles/PMC9482900/ /pubmed/35779185 http://dx.doi.org/10.1007/s10495-022-01747-8 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/) . |
spellingShingle | Article Zhang, Fei Luo, Hong Peng, Wuxun Wang, Lei Wang, Tao Xie, Zhihong Zhang, Jian Dong, Wentao Zheng, Xiaohan Liu, Gang Zhu, Xuesong Kang, Qinglin Tian, Xiaobin Hypoxic condition induced H3K27me3 modification of the LncRNA Tmem235 promoter thus supporting apoptosis of BMSCs |
title | Hypoxic condition induced H3K27me3 modification of the LncRNA Tmem235 promoter thus supporting apoptosis of BMSCs |
title_full | Hypoxic condition induced H3K27me3 modification of the LncRNA Tmem235 promoter thus supporting apoptosis of BMSCs |
title_fullStr | Hypoxic condition induced H3K27me3 modification of the LncRNA Tmem235 promoter thus supporting apoptosis of BMSCs |
title_full_unstemmed | Hypoxic condition induced H3K27me3 modification of the LncRNA Tmem235 promoter thus supporting apoptosis of BMSCs |
title_short | Hypoxic condition induced H3K27me3 modification of the LncRNA Tmem235 promoter thus supporting apoptosis of BMSCs |
title_sort | hypoxic condition induced h3k27me3 modification of the lncrna tmem235 promoter thus supporting apoptosis of bmscs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482900/ https://www.ncbi.nlm.nih.gov/pubmed/35779185 http://dx.doi.org/10.1007/s10495-022-01747-8 |
work_keys_str_mv | AT zhangfei hypoxicconditioninducedh3k27me3modificationofthelncrnatmem235promoterthussupportingapoptosisofbmscs AT luohong hypoxicconditioninducedh3k27me3modificationofthelncrnatmem235promoterthussupportingapoptosisofbmscs AT pengwuxun hypoxicconditioninducedh3k27me3modificationofthelncrnatmem235promoterthussupportingapoptosisofbmscs AT wanglei hypoxicconditioninducedh3k27me3modificationofthelncrnatmem235promoterthussupportingapoptosisofbmscs AT wangtao hypoxicconditioninducedh3k27me3modificationofthelncrnatmem235promoterthussupportingapoptosisofbmscs AT xiezhihong hypoxicconditioninducedh3k27me3modificationofthelncrnatmem235promoterthussupportingapoptosisofbmscs AT zhangjian hypoxicconditioninducedh3k27me3modificationofthelncrnatmem235promoterthussupportingapoptosisofbmscs AT dongwentao hypoxicconditioninducedh3k27me3modificationofthelncrnatmem235promoterthussupportingapoptosisofbmscs AT zhengxiaohan hypoxicconditioninducedh3k27me3modificationofthelncrnatmem235promoterthussupportingapoptosisofbmscs AT liugang hypoxicconditioninducedh3k27me3modificationofthelncrnatmem235promoterthussupportingapoptosisofbmscs AT zhuxuesong hypoxicconditioninducedh3k27me3modificationofthelncrnatmem235promoterthussupportingapoptosisofbmscs AT kangqinglin hypoxicconditioninducedh3k27me3modificationofthelncrnatmem235promoterthussupportingapoptosisofbmscs AT tianxiaobin hypoxicconditioninducedh3k27me3modificationofthelncrnatmem235promoterthussupportingapoptosisofbmscs |