EZH2-TROAP Pathway Promotes Prostate Cancer Progression Via TWIST Signals
Trophinin-associated protein (TROAP) has been shown to be overexpressed and promotes tumor progression in some tumors. We performed this study to assess the biological and clinical significance of TROAP in prostate cancer. We downloaded TROAP mRNA expression data from TCGA and GEO databases. We anal...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.592239/full |
| _version_ | 1818953472053084160 |
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| author | Lu Jin Yibin Zhou Guangqiang Chen Guangcheng Dai Kai Fu Dongrong Yang Jin Zhu |
| author_facet | Lu Jin Yibin Zhou Guangqiang Chen Guangcheng Dai Kai Fu Dongrong Yang Jin Zhu |
| author_sort | Lu Jin |
| collection | DOAJ |
| description | Trophinin-associated protein (TROAP) has been shown to be overexpressed and promotes tumor progression in some tumors. We performed this study to assess the biological and clinical significance of TROAP in prostate cancer. We downloaded TROAP mRNA expression data from TCGA and GEO databases. We analyzed expressions of TROAP and other genes in prostate cancer tumors at different stages and assessed Gleason scores. We used Celigo image, Transwell, and rescue assays, and flow cytometry detection to assess growth, apoptosis, proliferation, migration, and invasion of the prostate cancer cells. We identified and validated up- and down-stream genes in the TROAP pathway. The mRNA data suggested that TROAP expression was markedly upregulated in prostate cancer compared with its expression in normal tissues, especially in cancers with high stages and Gleason scores. Moreover, a high TROAP expression was associated with poor patient survival. Results of our in vitro assay showed that TROAP knockdown inhibited DU145 and PC3 cell proliferation and viability via cell apoptosis and S phase cycle arrest. The Transwell assay showed that TROAP knockdown inhibited cell migration and invasion, probably through MMP-9 and E-Cadherin modulation. Overexpression of TWIST partially abrogated the inhibitory effects of TROAP knockdown on prostate cancer cells. Our integrative mechanism dissection revealed that TROAP is in a pathway downstream of EZH2 and that it activates the TWIST/c-Myc pathway to regulate prostate cancer progression. In all, we identified TROAP as a driver of prostate cancer development and progression, providing a novel target for prostate cancer treatments. |
| first_indexed | 2024-12-20T10:06:49Z |
| format | Article |
| id | doaj.art-8a2df9d4f4bf469b8e79c23590f0ec3a |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T10:06:49Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8a2df9d4f4bf469b8e79c23590f0ec3a2022-12-21T19:44:13ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-02-011010.3389/fonc.2020.592239592239EZH2-TROAP Pathway Promotes Prostate Cancer Progression Via TWIST SignalsLu Jin0Yibin Zhou1Guangqiang Chen2Guangcheng Dai3Kai Fu4Dongrong Yang5Jin Zhu6Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Urology, Second Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Radiology, Second Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Urology, Second Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Urology, Second Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Urology, Second Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Urology, Second Affiliated Hospital of Soochow University, Suzhou, ChinaTrophinin-associated protein (TROAP) has been shown to be overexpressed and promotes tumor progression in some tumors. We performed this study to assess the biological and clinical significance of TROAP in prostate cancer. We downloaded TROAP mRNA expression data from TCGA and GEO databases. We analyzed expressions of TROAP and other genes in prostate cancer tumors at different stages and assessed Gleason scores. We used Celigo image, Transwell, and rescue assays, and flow cytometry detection to assess growth, apoptosis, proliferation, migration, and invasion of the prostate cancer cells. We identified and validated up- and down-stream genes in the TROAP pathway. The mRNA data suggested that TROAP expression was markedly upregulated in prostate cancer compared with its expression in normal tissues, especially in cancers with high stages and Gleason scores. Moreover, a high TROAP expression was associated with poor patient survival. Results of our in vitro assay showed that TROAP knockdown inhibited DU145 and PC3 cell proliferation and viability via cell apoptosis and S phase cycle arrest. The Transwell assay showed that TROAP knockdown inhibited cell migration and invasion, probably through MMP-9 and E-Cadherin modulation. Overexpression of TWIST partially abrogated the inhibitory effects of TROAP knockdown on prostate cancer cells. Our integrative mechanism dissection revealed that TROAP is in a pathway downstream of EZH2 and that it activates the TWIST/c-Myc pathway to regulate prostate cancer progression. In all, we identified TROAP as a driver of prostate cancer development and progression, providing a novel target for prostate cancer treatments.https://www.frontiersin.org/articles/10.3389/fonc.2020.592239/fullprostate cancerEZH2TWISTc-Myctrophinin associated protein |
| spellingShingle | Lu Jin Yibin Zhou Guangqiang Chen Guangcheng Dai Kai Fu Dongrong Yang Jin Zhu EZH2-TROAP Pathway Promotes Prostate Cancer Progression Via TWIST Signals Frontiers in Oncology prostate cancer EZH2 TWIST c-Myc trophinin associated protein |
| title | EZH2-TROAP Pathway Promotes Prostate Cancer Progression Via TWIST Signals |
| title_full | EZH2-TROAP Pathway Promotes Prostate Cancer Progression Via TWIST Signals |
| title_fullStr | EZH2-TROAP Pathway Promotes Prostate Cancer Progression Via TWIST Signals |
| title_full_unstemmed | EZH2-TROAP Pathway Promotes Prostate Cancer Progression Via TWIST Signals |
| title_short | EZH2-TROAP Pathway Promotes Prostate Cancer Progression Via TWIST Signals |
| title_sort | ezh2 troap pathway promotes prostate cancer progression via twist signals |
| topic | prostate cancer EZH2 TWIST c-Myc trophinin associated protein |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.592239/full |
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