Cargando…
Suppression of steroid 5α-reductase type I promotes cellular apoptosis and autophagy via PI3K/Akt/mTOR pathway in multiple myeloma
Steroid 5α-reductase type I (SRD5A1) is a validated oncogene in many sex hormone-related cancers, but its role in multiple myeloma (MM) remains unknown. Based on gene expression profiling (GEP) of sequential MM samples during the disease course, we found that the aberrant expression of SRD5A1 was co...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904855/ https://www.ncbi.nlm.nih.gov/pubmed/33627630 http://dx.doi.org/10.1038/s41419-021-03510-4 |
_version_ | 1783655004080439296 |
---|---|
author | Dou, Renjie Qian, Jinjun Wu, Wei Zhang, Yanxin Yuan, Yuxia Guo, Mengjie Wei, Rongfang Yang, Shu Jurczyszyn, Artur Janz, Siegfried Beksac, Meral Gu, Chunyan Yang, Ye |
author_facet | Dou, Renjie Qian, Jinjun Wu, Wei Zhang, Yanxin Yuan, Yuxia Guo, Mengjie Wei, Rongfang Yang, Shu Jurczyszyn, Artur Janz, Siegfried Beksac, Meral Gu, Chunyan Yang, Ye |
author_sort | Dou, Renjie |
collection | PubMed |
description | Steroid 5α-reductase type I (SRD5A1) is a validated oncogene in many sex hormone-related cancers, but its role in multiple myeloma (MM) remains unknown. Based on gene expression profiling (GEP) of sequential MM samples during the disease course, we found that the aberrant expression of SRD5A1 was correlated with progression and poor prognosis in MM patients. In this study, the oncogenic roles of SRD5A1 were validated in human MM cell lines (ARP1 and H929) and the xenograft MM model as well as the 5TMM mouse model. MTT and flow cytometry were used to assess MM cell proliferation, cell cycle, and apoptosis post inducible knockdown SRD5A1 by lentivirus-mediated short-hairpin RNA (shRNA). Transcriptomic sequencing, immunofluorescence, and western blot were used to investigate the effects of SRD5A1 suppression on cell apoptosis and autophagy. Mechanistically, SRD5A1 downregulation simultaneously regulated both the Bcl-2 family protein-mediated apoptosis and the autophagic process via PI3K/Akt/mTOR signaling pathway in MM cells. Meanwhile, the autophagy inhibitor (3-methyladenine) and SRD5A1 inhibitor (Dutasteride) were utilized to evaluate their anti-myeloma effect. Thus, our results demonstrated that SRD5A1 downregulation simultaneously regulated both the apoptosis and the autophagic process in MM cells. The dual autophagy–apoptosis regulatory SRD5A1 may serve as a biomarker and potential target for MM progression and prognosis. |
format | Online Article Text |
id | pubmed-7904855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79048552021-03-11 Suppression of steroid 5α-reductase type I promotes cellular apoptosis and autophagy via PI3K/Akt/mTOR pathway in multiple myeloma Dou, Renjie Qian, Jinjun Wu, Wei Zhang, Yanxin Yuan, Yuxia Guo, Mengjie Wei, Rongfang Yang, Shu Jurczyszyn, Artur Janz, Siegfried Beksac, Meral Gu, Chunyan Yang, Ye Cell Death Dis Article Steroid 5α-reductase type I (SRD5A1) is a validated oncogene in many sex hormone-related cancers, but its role in multiple myeloma (MM) remains unknown. Based on gene expression profiling (GEP) of sequential MM samples during the disease course, we found that the aberrant expression of SRD5A1 was correlated with progression and poor prognosis in MM patients. In this study, the oncogenic roles of SRD5A1 were validated in human MM cell lines (ARP1 and H929) and the xenograft MM model as well as the 5TMM mouse model. MTT and flow cytometry were used to assess MM cell proliferation, cell cycle, and apoptosis post inducible knockdown SRD5A1 by lentivirus-mediated short-hairpin RNA (shRNA). Transcriptomic sequencing, immunofluorescence, and western blot were used to investigate the effects of SRD5A1 suppression on cell apoptosis and autophagy. Mechanistically, SRD5A1 downregulation simultaneously regulated both the Bcl-2 family protein-mediated apoptosis and the autophagic process via PI3K/Akt/mTOR signaling pathway in MM cells. Meanwhile, the autophagy inhibitor (3-methyladenine) and SRD5A1 inhibitor (Dutasteride) were utilized to evaluate their anti-myeloma effect. Thus, our results demonstrated that SRD5A1 downregulation simultaneously regulated both the apoptosis and the autophagic process in MM cells. The dual autophagy–apoptosis regulatory SRD5A1 may serve as a biomarker and potential target for MM progression and prognosis. Nature Publishing Group UK 2021-02-24 /pmc/articles/PMC7904855/ /pubmed/33627630 http://dx.doi.org/10.1038/s41419-021-03510-4 Text en © The Author(s) 2021 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Dou, Renjie Qian, Jinjun Wu, Wei Zhang, Yanxin Yuan, Yuxia Guo, Mengjie Wei, Rongfang Yang, Shu Jurczyszyn, Artur Janz, Siegfried Beksac, Meral Gu, Chunyan Yang, Ye Suppression of steroid 5α-reductase type I promotes cellular apoptosis and autophagy via PI3K/Akt/mTOR pathway in multiple myeloma |
title | Suppression of steroid 5α-reductase type I promotes cellular apoptosis and autophagy via PI3K/Akt/mTOR pathway in multiple myeloma |
title_full | Suppression of steroid 5α-reductase type I promotes cellular apoptosis and autophagy via PI3K/Akt/mTOR pathway in multiple myeloma |
title_fullStr | Suppression of steroid 5α-reductase type I promotes cellular apoptosis and autophagy via PI3K/Akt/mTOR pathway in multiple myeloma |
title_full_unstemmed | Suppression of steroid 5α-reductase type I promotes cellular apoptosis and autophagy via PI3K/Akt/mTOR pathway in multiple myeloma |
title_short | Suppression of steroid 5α-reductase type I promotes cellular apoptosis and autophagy via PI3K/Akt/mTOR pathway in multiple myeloma |
title_sort | suppression of steroid 5α-reductase type i promotes cellular apoptosis and autophagy via pi3k/akt/mtor pathway in multiple myeloma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904855/ https://www.ncbi.nlm.nih.gov/pubmed/33627630 http://dx.doi.org/10.1038/s41419-021-03510-4 |
work_keys_str_mv | AT dourenjie suppressionofsteroid5areductasetypeipromotescellularapoptosisandautophagyviapi3kaktmtorpathwayinmultiplemyeloma AT qianjinjun suppressionofsteroid5areductasetypeipromotescellularapoptosisandautophagyviapi3kaktmtorpathwayinmultiplemyeloma AT wuwei suppressionofsteroid5areductasetypeipromotescellularapoptosisandautophagyviapi3kaktmtorpathwayinmultiplemyeloma AT zhangyanxin suppressionofsteroid5areductasetypeipromotescellularapoptosisandautophagyviapi3kaktmtorpathwayinmultiplemyeloma AT yuanyuxia suppressionofsteroid5areductasetypeipromotescellularapoptosisandautophagyviapi3kaktmtorpathwayinmultiplemyeloma AT guomengjie suppressionofsteroid5areductasetypeipromotescellularapoptosisandautophagyviapi3kaktmtorpathwayinmultiplemyeloma AT weirongfang suppressionofsteroid5areductasetypeipromotescellularapoptosisandautophagyviapi3kaktmtorpathwayinmultiplemyeloma AT yangshu suppressionofsteroid5areductasetypeipromotescellularapoptosisandautophagyviapi3kaktmtorpathwayinmultiplemyeloma AT jurczyszynartur suppressionofsteroid5areductasetypeipromotescellularapoptosisandautophagyviapi3kaktmtorpathwayinmultiplemyeloma AT janzsiegfried suppressionofsteroid5areductasetypeipromotescellularapoptosisandautophagyviapi3kaktmtorpathwayinmultiplemyeloma AT beksacmeral suppressionofsteroid5areductasetypeipromotescellularapoptosisandautophagyviapi3kaktmtorpathwayinmultiplemyeloma AT guchunyan suppressionofsteroid5areductasetypeipromotescellularapoptosisandautophagyviapi3kaktmtorpathwayinmultiplemyeloma AT yangye suppressionofsteroid5areductasetypeipromotescellularapoptosisandautophagyviapi3kaktmtorpathwayinmultiplemyeloma |