Cargando…
miR-22 protect PC12 from ischemia/reperfusion-induced injury by targeting p53 upregulated modulator of apoptosis (PUMA)
MicroRNAs have been implicated as critical regulatory molecules in many cerebrovascular diseases. Recent studies demonstrated miR-22 might provide a potential neuroprotective effect. However, the neuroprotective effect of miR-22 in ischemia/reperfusion (I/R) injury has not been thoroughly elucidated...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039629/ https://www.ncbi.nlm.nih.gov/pubmed/32065044 http://dx.doi.org/10.1080/21655979.2020.1729321 |
_version_ | 1783500839535509504 |
---|---|
author | Jiao, Hongmei Chen, Renyi Jiang, Ziru Zhang, Lin Wang, Hongwei |
author_facet | Jiao, Hongmei Chen, Renyi Jiang, Ziru Zhang, Lin Wang, Hongwei |
author_sort | Jiao, Hongmei |
collection | PubMed |
description | MicroRNAs have been implicated as critical regulatory molecules in many cerebrovascular diseases. Recent studies demonstrated miR-22 might provide a potential neuroprotective effect. However, the neuroprotective effect of miR-22 in ischemia/reperfusion (I/R) injury has not been thoroughly elucidated. In this study, the PC12 cells were subjected to 4 h oxygen and glucose deprivation (I) and 24 h reoxygenation (R). The PC12 cells were pre-transfected with miR-22 or anti-miR-22 or siRNA-mediated downregulation of p53-upregulated-modulator-of-apoptosis (PUMA)(PUMA siRNA) or their controls at 24 h prior to exposure to I/R. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot were employed to analyze mRNA and protein expression. PI and Annexin V assays and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay were used to quantify the rate of apoptosis. We found that miR-22 expression was significantly downregulated in the PC12 cells subjected to I/R. Loss of function of miR-22 increased PC12 apoptosis after I/R, and overexpression of miR-22 decreases PC12 apoptosis after I/R. PUMA protein was upregulated in the I/R group as compared with the sham group. The increased PUMA protein expression and apoptosis induced by I/R was reversed by transfection with PUMA siRNA. We concluded that I/R enhanced apoptosis and PUMA expression in PC12 cells via downregulation of miR-22. Enhanced miR-22 expression reversed both PUMA expression and apoptosis induced by I/R in PC12 cells. miR-22/PUMA axis has important implications for their clinical applications. |
format | Online Article Text |
id | pubmed-7039629 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-70396292021-02-15 miR-22 protect PC12 from ischemia/reperfusion-induced injury by targeting p53 upregulated modulator of apoptosis (PUMA) Jiao, Hongmei Chen, Renyi Jiang, Ziru Zhang, Lin Wang, Hongwei Bioengineered Research Paper MicroRNAs have been implicated as critical regulatory molecules in many cerebrovascular diseases. Recent studies demonstrated miR-22 might provide a potential neuroprotective effect. However, the neuroprotective effect of miR-22 in ischemia/reperfusion (I/R) injury has not been thoroughly elucidated. In this study, the PC12 cells were subjected to 4 h oxygen and glucose deprivation (I) and 24 h reoxygenation (R). The PC12 cells were pre-transfected with miR-22 or anti-miR-22 or siRNA-mediated downregulation of p53-upregulated-modulator-of-apoptosis (PUMA)(PUMA siRNA) or their controls at 24 h prior to exposure to I/R. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot were employed to analyze mRNA and protein expression. PI and Annexin V assays and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay were used to quantify the rate of apoptosis. We found that miR-22 expression was significantly downregulated in the PC12 cells subjected to I/R. Loss of function of miR-22 increased PC12 apoptosis after I/R, and overexpression of miR-22 decreases PC12 apoptosis after I/R. PUMA protein was upregulated in the I/R group as compared with the sham group. The increased PUMA protein expression and apoptosis induced by I/R was reversed by transfection with PUMA siRNA. We concluded that I/R enhanced apoptosis and PUMA expression in PC12 cells via downregulation of miR-22. Enhanced miR-22 expression reversed both PUMA expression and apoptosis induced by I/R in PC12 cells. miR-22/PUMA axis has important implications for their clinical applications. Taylor & Francis 2020-02-15 /pmc/articles/PMC7039629/ /pubmed/32065044 http://dx.doi.org/10.1080/21655979.2020.1729321 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Jiao, Hongmei Chen, Renyi Jiang, Ziru Zhang, Lin Wang, Hongwei miR-22 protect PC12 from ischemia/reperfusion-induced injury by targeting p53 upregulated modulator of apoptosis (PUMA) |
title | miR-22 protect PC12 from ischemia/reperfusion-induced injury by targeting p53 upregulated modulator of apoptosis (PUMA) |
title_full | miR-22 protect PC12 from ischemia/reperfusion-induced injury by targeting p53 upregulated modulator of apoptosis (PUMA) |
title_fullStr | miR-22 protect PC12 from ischemia/reperfusion-induced injury by targeting p53 upregulated modulator of apoptosis (PUMA) |
title_full_unstemmed | miR-22 protect PC12 from ischemia/reperfusion-induced injury by targeting p53 upregulated modulator of apoptosis (PUMA) |
title_short | miR-22 protect PC12 from ischemia/reperfusion-induced injury by targeting p53 upregulated modulator of apoptosis (PUMA) |
title_sort | mir-22 protect pc12 from ischemia/reperfusion-induced injury by targeting p53 upregulated modulator of apoptosis (puma) |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039629/ https://www.ncbi.nlm.nih.gov/pubmed/32065044 http://dx.doi.org/10.1080/21655979.2020.1729321 |
work_keys_str_mv | AT jiaohongmei mir22protectpc12fromischemiareperfusioninducedinjurybytargetingp53upregulatedmodulatorofapoptosispuma AT chenrenyi mir22protectpc12fromischemiareperfusioninducedinjurybytargetingp53upregulatedmodulatorofapoptosispuma AT jiangziru mir22protectpc12fromischemiareperfusioninducedinjurybytargetingp53upregulatedmodulatorofapoptosispuma AT zhanglin mir22protectpc12fromischemiareperfusioninducedinjurybytargetingp53upregulatedmodulatorofapoptosispuma AT wanghongwei mir22protectpc12fromischemiareperfusioninducedinjurybytargetingp53upregulatedmodulatorofapoptosispuma |