The HMGB1-2 Ovarian Cancer Interactome. The Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response
High mobility group box B (HMGB) proteins are overexpressed in different types of cancers such as epithelial ovarian cancers (EOC). We have determined the first interactome of HMGB1 and HMGB2 in epithelial ovarian cancer (the EOC-HMGB interactome). Libraries from the SKOV-3 cell line and a primary t...
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MDPI AG
2020-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/9/2435 |
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| author | María Cámara-Quílez Aida Barreiro-Alonso Ángel Vizoso-Vázquez Esther Rodríguez-Belmonte María Quindós-Varela Mónica Lamas-Maceiras María Esperanza Cerdán |
| author_facet | María Cámara-Quílez Aida Barreiro-Alonso Ángel Vizoso-Vázquez Esther Rodríguez-Belmonte María Quindós-Varela Mónica Lamas-Maceiras María Esperanza Cerdán |
| author_sort | María Cámara-Quílez |
| collection | DOAJ |
| description | High mobility group box B (HMGB) proteins are overexpressed in different types of cancers such as epithelial ovarian cancers (EOC). We have determined the first interactome of HMGB1 and HMGB2 in epithelial ovarian cancer (the EOC-HMGB interactome). Libraries from the SKOV-3 cell line and a primary transitional cell carcinoma (TCC) ovarian tumor were tested by the Yeast Two Hybrid (Y2H) approach. The interactome reveals proteins that are related to cancer hallmarks and their expression is altered in EOC. Moreover, some of these proteins have been associated to survival and prognosis of patients. The interaction of MIEN1 and NOP53 with HMGB2 has been validated by co-immunoprecipitation in SKOV-3 and PEO1 cell lines. SKOV-3 cells were treated with different anti-tumoral drugs to evaluate changes in HMGB1, HMGB2, MIEN1 and NOP53 gene expression. Results show that combined treatment of paclitaxel and carboplatin induces a stronger down-regulation of these genes in comparison to individual treatments. Individual treatment with paclitaxel or olaparib up-regulates NOP53, which is expressed at lower levels in EOC than in non-cancerous cells. On the other hand, bevacizumab diminishes the expression of HMGB2 and NOP53. This study also shows that silencing of these genes affects cell-viability after drug exposure. HMGB1 silencing causes loss of response to paclitaxel, whereas silencing of HMGB2 slightly increases sensitivity to olaparib. Silencing of either HMGB1 or HMGB2 increases sensitivity to carboplatin. Lastly, a moderate loss of response to bevacizumab is observed when NOP53 is silenced. |
| first_indexed | 2024-03-10T16:46:56Z |
| format | Article |
| id | doaj.art-77c5cddfe64641899d835f5802d5b986 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T16:46:56Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-77c5cddfe64641899d835f5802d5b9862023-11-20T11:33:15ZengMDPI AGCancers2072-66942020-08-01129243510.3390/cancers12092435The HMGB1-2 Ovarian Cancer Interactome. The Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-ResponseMaría Cámara-Quílez0Aida Barreiro-Alonso1Ángel Vizoso-Vázquez2Esther Rodríguez-Belmonte3María Quindós-Varela4Mónica Lamas-Maceiras5María Esperanza Cerdán6Department of Biology, EXPRELA Group, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Bioloxía, Facultade de Ciencias, INIBIC- Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, SpainDepartment of Biology, EXPRELA Group, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Bioloxía, Facultade de Ciencias, INIBIC- Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, SpainDepartment of Biology, EXPRELA Group, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Bioloxía, Facultade de Ciencias, INIBIC- Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, SpainDepartment of Biology, EXPRELA Group, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Bioloxía, Facultade de Ciencias, INIBIC- Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, SpainDepartment of Oncology, Translational Cancer Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Carretera del Pasaje s/n, 15006 A Coruña, SpainDepartment of Biology, EXPRELA Group, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Bioloxía, Facultade de Ciencias, INIBIC- Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, SpainDepartment of Biology, EXPRELA Group, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Bioloxía, Facultade de Ciencias, INIBIC- Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, SpainHigh mobility group box B (HMGB) proteins are overexpressed in different types of cancers such as epithelial ovarian cancers (EOC). We have determined the first interactome of HMGB1 and HMGB2 in epithelial ovarian cancer (the EOC-HMGB interactome). Libraries from the SKOV-3 cell line and a primary transitional cell carcinoma (TCC) ovarian tumor were tested by the Yeast Two Hybrid (Y2H) approach. The interactome reveals proteins that are related to cancer hallmarks and their expression is altered in EOC. Moreover, some of these proteins have been associated to survival and prognosis of patients. The interaction of MIEN1 and NOP53 with HMGB2 has been validated by co-immunoprecipitation in SKOV-3 and PEO1 cell lines. SKOV-3 cells were treated with different anti-tumoral drugs to evaluate changes in HMGB1, HMGB2, MIEN1 and NOP53 gene expression. Results show that combined treatment of paclitaxel and carboplatin induces a stronger down-regulation of these genes in comparison to individual treatments. Individual treatment with paclitaxel or olaparib up-regulates NOP53, which is expressed at lower levels in EOC than in non-cancerous cells. On the other hand, bevacizumab diminishes the expression of HMGB2 and NOP53. This study also shows that silencing of these genes affects cell-viability after drug exposure. HMGB1 silencing causes loss of response to paclitaxel, whereas silencing of HMGB2 slightly increases sensitivity to olaparib. Silencing of either HMGB1 or HMGB2 increases sensitivity to carboplatin. Lastly, a moderate loss of response to bevacizumab is observed when NOP53 is silenced.https://www.mdpi.com/2072-6694/12/9/2435ovarian cancerinteractomechemotherapy |
| spellingShingle | María Cámara-Quílez Aida Barreiro-Alonso Ángel Vizoso-Vázquez Esther Rodríguez-Belmonte María Quindós-Varela Mónica Lamas-Maceiras María Esperanza Cerdán The HMGB1-2 Ovarian Cancer Interactome. The Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response Cancers ovarian cancer interactome chemotherapy |
| title | The HMGB1-2 Ovarian Cancer Interactome. The Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response |
| title_full | The HMGB1-2 Ovarian Cancer Interactome. The Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response |
| title_fullStr | The HMGB1-2 Ovarian Cancer Interactome. The Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response |
| title_full_unstemmed | The HMGB1-2 Ovarian Cancer Interactome. The Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response |
| title_short | The HMGB1-2 Ovarian Cancer Interactome. The Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response |
| title_sort | hmgb1 2 ovarian cancer interactome the role of hmgb proteins and their interacting partners mien1 and nop53 in ovary cancer and drug response |
| topic | ovarian cancer interactome chemotherapy |
| url | https://www.mdpi.com/2072-6694/12/9/2435 |
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