Androgen up-regulation of Twist1 gene expression is mediated by ETV1
Twist1, a basic helix-loop-helix transcription factor that regulates a number of genes involved in epithelial-to-mesenchymal transition (EMT), is upregulated in prostate cancer. Androgen regulation of Twist1 has been reported in a previous study. However, the mechanism of androgen regulation of the...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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PeerJ Inc.
2020-04-01
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| Series: | PeerJ |
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| Online Access: | https://peerj.com/articles/8921.pdf |
| _version_ | 1797423832924946432 |
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| author | Prabesh Khatiwada Archana Kannan Mamata Malla Megan Dreier Lirim Shemshedini |
| author_facet | Prabesh Khatiwada Archana Kannan Mamata Malla Megan Dreier Lirim Shemshedini |
| author_sort | Prabesh Khatiwada |
| collection | DOAJ |
| description | Twist1, a basic helix-loop-helix transcription factor that regulates a number of genes involved in epithelial-to-mesenchymal transition (EMT), is upregulated in prostate cancer. Androgen regulation of Twist1 has been reported in a previous study. However, the mechanism of androgen regulation of the Twist1 gene is not understood because the Twist1 promoter lacks androgen receptor (AR)-responsive elements. Previous studies have shown that the Twist1 promoter has putative binding sites for PEA3 subfamily of ETS transcription factors. Our lab has previously identified Ets Variant 1 (ETV1), a member of the PEA3 subfamily, as a novel androgen-regulated gene that is involved in prostate cancer cell invasion through unknown mechanism. In view of these data, we hypothesized that androgen-activated AR upregulates Twist1 gene expression via ETV1. Our data confirmed the published work that androgen positively regulates Twist1 gene expression and further showed that this positive effect was directed at the Twist1 promoter. The positive effect of androgen on Twist1 gene expression was abrogated upon disruption of AR expression by siRNA or of AR activity by Casodex. More importantly, our data show that disruption of ETV1 leads to significant decrease in both androgen-mediated upregulation as well as basal level of Twist1, which we are able to rescue upon re-expression of ETV1. Indeed, we are able to show that ETV1 mediates the androgen upregulation of Twist1 by acting on the proximal region of Twist1 promoter. Additionally, our data show that Twist1 regulates prostate cancer cell invasion and EMT, providing a possible mechanism by which ETV1 mediates prostate cancer cell invasion. In conclusion, in this study we report Twist1 as an indirect target of AR and androgen regulation through ETV1. |
| first_indexed | 2024-03-09T07:53:29Z |
| format | Article |
| id | doaj.art-4b39497428504500b3e873b7e9b9e6b8 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T07:53:29Z |
| publishDate | 2020-04-01 |
| publisher | PeerJ Inc. |
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| series | PeerJ |
| spelling | doaj.art-4b39497428504500b3e873b7e9b9e6b82023-12-03T01:20:53ZengPeerJ Inc.PeerJ2167-83592020-04-018e892110.7717/peerj.8921Androgen up-regulation of Twist1 gene expression is mediated by ETV1Prabesh KhatiwadaArchana KannanMamata MallaMegan DreierLirim ShemshediniTwist1, a basic helix-loop-helix transcription factor that regulates a number of genes involved in epithelial-to-mesenchymal transition (EMT), is upregulated in prostate cancer. Androgen regulation of Twist1 has been reported in a previous study. However, the mechanism of androgen regulation of the Twist1 gene is not understood because the Twist1 promoter lacks androgen receptor (AR)-responsive elements. Previous studies have shown that the Twist1 promoter has putative binding sites for PEA3 subfamily of ETS transcription factors. Our lab has previously identified Ets Variant 1 (ETV1), a member of the PEA3 subfamily, as a novel androgen-regulated gene that is involved in prostate cancer cell invasion through unknown mechanism. In view of these data, we hypothesized that androgen-activated AR upregulates Twist1 gene expression via ETV1. Our data confirmed the published work that androgen positively regulates Twist1 gene expression and further showed that this positive effect was directed at the Twist1 promoter. The positive effect of androgen on Twist1 gene expression was abrogated upon disruption of AR expression by siRNA or of AR activity by Casodex. More importantly, our data show that disruption of ETV1 leads to significant decrease in both androgen-mediated upregulation as well as basal level of Twist1, which we are able to rescue upon re-expression of ETV1. Indeed, we are able to show that ETV1 mediates the androgen upregulation of Twist1 by acting on the proximal region of Twist1 promoter. Additionally, our data show that Twist1 regulates prostate cancer cell invasion and EMT, providing a possible mechanism by which ETV1 mediates prostate cancer cell invasion. In conclusion, in this study we report Twist1 as an indirect target of AR and androgen regulation through ETV1.https://peerj.com/articles/8921.pdfAndrogenAndrogen receptorTwist1ETV1MetastasisProstate cancer |
| spellingShingle | Prabesh Khatiwada Archana Kannan Mamata Malla Megan Dreier Lirim Shemshedini Androgen up-regulation of Twist1 gene expression is mediated by ETV1 PeerJ Androgen Androgen receptor Twist1 ETV1 Metastasis Prostate cancer |
| title | Androgen up-regulation of Twist1 gene expression is mediated by ETV1 |
| title_full | Androgen up-regulation of Twist1 gene expression is mediated by ETV1 |
| title_fullStr | Androgen up-regulation of Twist1 gene expression is mediated by ETV1 |
| title_full_unstemmed | Androgen up-regulation of Twist1 gene expression is mediated by ETV1 |
| title_short | Androgen up-regulation of Twist1 gene expression is mediated by ETV1 |
| title_sort | androgen up regulation of twist1 gene expression is mediated by etv1 |
| topic | Androgen Androgen receptor Twist1 ETV1 Metastasis Prostate cancer |
| url | https://peerj.com/articles/8921.pdf |
| work_keys_str_mv | AT prabeshkhatiwada androgenupregulationoftwist1geneexpressionismediatedbyetv1 AT archanakannan androgenupregulationoftwist1geneexpressionismediatedbyetv1 AT mamatamalla androgenupregulationoftwist1geneexpressionismediatedbyetv1 AT megandreier androgenupregulationoftwist1geneexpressionismediatedbyetv1 AT lirimshemshedini androgenupregulationoftwist1geneexpressionismediatedbyetv1 |