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VPS33B interacts with NESG1 to suppress cell growth and cisplatin chemoresistance in ovarian cancer
The pathogenesis and cisplatin chemoresistance of ovarian cancer (OC) are still unclear. Vacuolar protein sorting‐associated 33B (VPS33B) has not been reported in OC to date. In this study, immunohistochemistry was used to detect VPS33B protein expression between OC and ovarian tissues. MTT, EdU, co...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088924/ https://www.ncbi.nlm.nih.gov/pubmed/33788346 http://dx.doi.org/10.1111/cas.14864 |
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author | Ning, Yingxia Zeng, Zhaoyang Deng, Yuao Feng, Weifeng Huang, Lun Liu, Huiling Lin, Jiazhi Zhang, Chen Fan, Yue Liu, Longyang |
author_facet | Ning, Yingxia Zeng, Zhaoyang Deng, Yuao Feng, Weifeng Huang, Lun Liu, Huiling Lin, Jiazhi Zhang, Chen Fan, Yue Liu, Longyang |
author_sort | Ning, Yingxia |
collection | PubMed |
description | The pathogenesis and cisplatin chemoresistance of ovarian cancer (OC) are still unclear. Vacuolar protein sorting‐associated 33B (VPS33B) has not been reported in OC to date. In this study, immunohistochemistry was used to detect VPS33B protein expression between OC and ovarian tissues. MTT, EdU, colony formation, cell cycle, in vivo tumorigenesis, western blot, ChIP, EMSA, co‐immunoprecipitation (CoIP), qRT‐PCR, and microconfocal microscopy were used to explore the function and molecular mechanisms of VPS33B in OC cells. The results of the present study demonstrated that VPS33B protein expression was obviously reduced in OC compared with that in ovarian tissues. Overexpressed VPS33B suppressed cell cycle transition, cell growth, and chemoresistance to cisplatin in vitro and in vivo. Analysis of the mechanism indicated that overexpressed VPS33B regulated the epidermal growth factor receptor (EGFR)/PI3K/AKT/c‐Myc/p53/miR‐133a‐3p feedback loop and reduced the expression of the cell cycle factor CDK4. Nasopharyngeal epithelium‐specific protein 1 (NESG1) as a tumor suppressor not only interacted with VPS33B, but was also induced by VPS33B by the attenuation of PI3K/AKT/c‐Jun‐mediated transcription inhibition. Overexpressed NESG1 further suppressed cell growth by mediating VPS33B‐modulated signals in VPS33B‐overexpressing OC cells. Finally, NESG1 induced VPS33B expression by reducing the inhibition of PI3K/AKT/c‐Jun‐mediated transcription. Our study is the first to demonstrate that VPS33B serves as a tumor suppressor, and VPS33B can interact with NESG1 to suppress cell growth and promote cisplatin sensitivity by regulating the EGFR/PI3K/AKT/c‐Myc/p53/miR‐133a‐3p feedback loop in OC cells. |
format | Online Article Text |
id | pubmed-8088924 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80889242021-05-10 VPS33B interacts with NESG1 to suppress cell growth and cisplatin chemoresistance in ovarian cancer Ning, Yingxia Zeng, Zhaoyang Deng, Yuao Feng, Weifeng Huang, Lun Liu, Huiling Lin, Jiazhi Zhang, Chen Fan, Yue Liu, Longyang Cancer Sci Original Articles The pathogenesis and cisplatin chemoresistance of ovarian cancer (OC) are still unclear. Vacuolar protein sorting‐associated 33B (VPS33B) has not been reported in OC to date. In this study, immunohistochemistry was used to detect VPS33B protein expression between OC and ovarian tissues. MTT, EdU, colony formation, cell cycle, in vivo tumorigenesis, western blot, ChIP, EMSA, co‐immunoprecipitation (CoIP), qRT‐PCR, and microconfocal microscopy were used to explore the function and molecular mechanisms of VPS33B in OC cells. The results of the present study demonstrated that VPS33B protein expression was obviously reduced in OC compared with that in ovarian tissues. Overexpressed VPS33B suppressed cell cycle transition, cell growth, and chemoresistance to cisplatin in vitro and in vivo. Analysis of the mechanism indicated that overexpressed VPS33B regulated the epidermal growth factor receptor (EGFR)/PI3K/AKT/c‐Myc/p53/miR‐133a‐3p feedback loop and reduced the expression of the cell cycle factor CDK4. Nasopharyngeal epithelium‐specific protein 1 (NESG1) as a tumor suppressor not only interacted with VPS33B, but was also induced by VPS33B by the attenuation of PI3K/AKT/c‐Jun‐mediated transcription inhibition. Overexpressed NESG1 further suppressed cell growth by mediating VPS33B‐modulated signals in VPS33B‐overexpressing OC cells. Finally, NESG1 induced VPS33B expression by reducing the inhibition of PI3K/AKT/c‐Jun‐mediated transcription. Our study is the first to demonstrate that VPS33B serves as a tumor suppressor, and VPS33B can interact with NESG1 to suppress cell growth and promote cisplatin sensitivity by regulating the EGFR/PI3K/AKT/c‐Myc/p53/miR‐133a‐3p feedback loop in OC cells. John Wiley and Sons Inc. 2021-03-31 2021-05 /pmc/articles/PMC8088924/ /pubmed/33788346 http://dx.doi.org/10.1111/cas.14864 Text en © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Ning, Yingxia Zeng, Zhaoyang Deng, Yuao Feng, Weifeng Huang, Lun Liu, Huiling Lin, Jiazhi Zhang, Chen Fan, Yue Liu, Longyang VPS33B interacts with NESG1 to suppress cell growth and cisplatin chemoresistance in ovarian cancer |
title | VPS33B interacts with NESG1 to suppress cell growth and cisplatin chemoresistance in ovarian cancer |
title_full | VPS33B interacts with NESG1 to suppress cell growth and cisplatin chemoresistance in ovarian cancer |
title_fullStr | VPS33B interacts with NESG1 to suppress cell growth and cisplatin chemoresistance in ovarian cancer |
title_full_unstemmed | VPS33B interacts with NESG1 to suppress cell growth and cisplatin chemoresistance in ovarian cancer |
title_short | VPS33B interacts with NESG1 to suppress cell growth and cisplatin chemoresistance in ovarian cancer |
title_sort | vps33b interacts with nesg1 to suppress cell growth and cisplatin chemoresistance in ovarian cancer |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088924/ https://www.ncbi.nlm.nih.gov/pubmed/33788346 http://dx.doi.org/10.1111/cas.14864 |
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