Downregulated miR-181a alleviates H2O2-induced oxidative stress and cellular senescence by targeting PDIA6 in human foreskin fibroblasts

Abstract Background Oxidative stress is strongly associated with cellular senescence. Numerous studies have indicated that microRNAs (miRNAs) play a critical part in cellular senescence. MiR-181a was reported to induce cellular senescence, however, the potential mechanism of miR-181a in hydrogen pe...

Full description

Bibliographic Details
Main Authors: Yan Huang, Huimin Yan, Yanqing Yang, Jinfei Zhou, Qijun Xu, Hu Meng
Format: Article
Language:English
Published: Sociedade Brasileira de Dermatologia 2023-04-01
Series:Anais Brasileiros de Dermatologia
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962023000100017&lng=en&tlng=en
_version_ 1797852874154180608
author Yan Huang
Huimin Yan
Yanqing Yang
Jinfei Zhou
Qijun Xu
Hu Meng
author_facet Yan Huang
Huimin Yan
Yanqing Yang
Jinfei Zhou
Qijun Xu
Hu Meng
author_sort Yan Huang
collection DOAJ
description Abstract Background Oxidative stress is strongly associated with cellular senescence. Numerous studies have indicated that microRNAs (miRNAs) play a critical part in cellular senescence. MiR-181a was reported to induce cellular senescence, however, the potential mechanism of miR-181a in hydrogen peroxide (H2O2)-induced cellular senescence remains obscure. Objective The aim of this study is to investigate the role and regulatory mechanism of miR-181a in H2O2-induced cellular senescence. Methods Human foreskin fibroblasts (HFF) transfected with miR-181a inhibitor/miR-NC with or without H2O2 treatment were divided into four groups: control + miR-NC/miR-181a inhibitor, H2O2 + miR-NC/miR-181a inhibitor. CCK-8 assay was utilized to evaluate the viability of HFF. RT-qPCR was used to measure the expression of miR-181a and its target genes. Protein levels of protein disulfide isomerase family A member 6 (PDIA6) and senescence markers were assessed by western blotting. Senescence-associated β-galactosidase (SA-β-gal) staining was applied for detecting SA-β-gal activity. The activities of SOD, GPx, and CAT were detected by corresponding assay kits. The binding relation between PDIA6 and miR-181a was identified by luciferase reporter assay. Results MiR-181a inhibition suppressed H2O2-induced oxidative stress and cellular senescence in HFF. PDIA6 was targeted by miR-181a and lowly expressed in H2O2-treated HFF. Knocking down PDIA6 reversed miR-181a inhibition-mediated suppressive impact on H2O2-induced oxidative stress and cellular senescence in HFF. Study limitations Signaling pathways that might be mediated by miR-181a/PDIA6 axis were not investigated. Conclusion Downregulated miR-181a attenuates H2O2-induced oxidative stress and cellular senescence in HFF by targeting PDIA6.
first_indexed 2024-04-09T19:41:22Z
format Article
id doaj.art-be7c82c82f5d45f09f7c84a825a11837
institution Directory Open Access Journal
issn 0365-0596
language English
last_indexed 2024-04-09T19:41:22Z
publishDate 2023-04-01
publisher Sociedade Brasileira de Dermatologia
record_format Article
series Anais Brasileiros de Dermatologia
spelling doaj.art-be7c82c82f5d45f09f7c84a825a118372023-04-04T07:34:40ZengSociedade Brasileira de DermatologiaAnais Brasileiros de Dermatologia0365-05962023-04-01981172510.1016/j.abd.2021.12.007Downregulated miR-181a alleviates H2O2-induced oxidative stress and cellular senescence by targeting PDIA6 in human foreskin fibroblastsYan Huanghttps://orcid.org/0000-0002-5536-0121Huimin Yanhttps://orcid.org/0000-0001-9533-6110Yanqing Yanghttps://orcid.org/0000-0002-7505-6282Jinfei Zhouhttps://orcid.org/0000-0002-0004-6290Qijun Xuhttps://orcid.org/0000-0001-7003-2719Hu Menghttps://orcid.org/0000-0001-7483-5957Abstract Background Oxidative stress is strongly associated with cellular senescence. Numerous studies have indicated that microRNAs (miRNAs) play a critical part in cellular senescence. MiR-181a was reported to induce cellular senescence, however, the potential mechanism of miR-181a in hydrogen peroxide (H2O2)-induced cellular senescence remains obscure. Objective The aim of this study is to investigate the role and regulatory mechanism of miR-181a in H2O2-induced cellular senescence. Methods Human foreskin fibroblasts (HFF) transfected with miR-181a inhibitor/miR-NC with or without H2O2 treatment were divided into four groups: control + miR-NC/miR-181a inhibitor, H2O2 + miR-NC/miR-181a inhibitor. CCK-8 assay was utilized to evaluate the viability of HFF. RT-qPCR was used to measure the expression of miR-181a and its target genes. Protein levels of protein disulfide isomerase family A member 6 (PDIA6) and senescence markers were assessed by western blotting. Senescence-associated β-galactosidase (SA-β-gal) staining was applied for detecting SA-β-gal activity. The activities of SOD, GPx, and CAT were detected by corresponding assay kits. The binding relation between PDIA6 and miR-181a was identified by luciferase reporter assay. Results MiR-181a inhibition suppressed H2O2-induced oxidative stress and cellular senescence in HFF. PDIA6 was targeted by miR-181a and lowly expressed in H2O2-treated HFF. Knocking down PDIA6 reversed miR-181a inhibition-mediated suppressive impact on H2O2-induced oxidative stress and cellular senescence in HFF. Study limitations Signaling pathways that might be mediated by miR-181a/PDIA6 axis were not investigated. Conclusion Downregulated miR-181a attenuates H2O2-induced oxidative stress and cellular senescence in HFF by targeting PDIA6.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962023000100017&lng=en&tlng=enCellular senescenceOxidative stressProtein disulfide-isomerases
spellingShingle Yan Huang
Huimin Yan
Yanqing Yang
Jinfei Zhou
Qijun Xu
Hu Meng
Downregulated miR-181a alleviates H2O2-induced oxidative stress and cellular senescence by targeting PDIA6 in human foreskin fibroblasts
Anais Brasileiros de Dermatologia
Cellular senescence
Oxidative stress
Protein disulfide-isomerases
title Downregulated miR-181a alleviates H2O2-induced oxidative stress and cellular senescence by targeting PDIA6 in human foreskin fibroblasts
title_full Downregulated miR-181a alleviates H2O2-induced oxidative stress and cellular senescence by targeting PDIA6 in human foreskin fibroblasts
title_fullStr Downregulated miR-181a alleviates H2O2-induced oxidative stress and cellular senescence by targeting PDIA6 in human foreskin fibroblasts
title_full_unstemmed Downregulated miR-181a alleviates H2O2-induced oxidative stress and cellular senescence by targeting PDIA6 in human foreskin fibroblasts
title_short Downregulated miR-181a alleviates H2O2-induced oxidative stress and cellular senescence by targeting PDIA6 in human foreskin fibroblasts
title_sort downregulated mir 181a alleviates h2o2 induced oxidative stress and cellular senescence by targeting pdia6 in human foreskin fibroblasts
topic Cellular senescence
Oxidative stress
Protein disulfide-isomerases
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962023000100017&lng=en&tlng=en
work_keys_str_mv AT yanhuang downregulatedmir181aalleviatesh2o2inducedoxidativestressandcellularsenescencebytargetingpdia6inhumanforeskinfibroblasts
AT huiminyan downregulatedmir181aalleviatesh2o2inducedoxidativestressandcellularsenescencebytargetingpdia6inhumanforeskinfibroblasts
AT yanqingyang downregulatedmir181aalleviatesh2o2inducedoxidativestressandcellularsenescencebytargetingpdia6inhumanforeskinfibroblasts
AT jinfeizhou downregulatedmir181aalleviatesh2o2inducedoxidativestressandcellularsenescencebytargetingpdia6inhumanforeskinfibroblasts
AT qijunxu downregulatedmir181aalleviatesh2o2inducedoxidativestressandcellularsenescencebytargetingpdia6inhumanforeskinfibroblasts
AT humeng downregulatedmir181aalleviatesh2o2inducedoxidativestressandcellularsenescencebytargetingpdia6inhumanforeskinfibroblasts