Novel role of BRCA1 interacting C‐terminal helicase 1 (<i>BRIP1</i>) in breast tumour cell invasion
<p dir="ltr">Breast cancer (BC) is the most common malignancy and the leading cause of death in women worldwide. Only 5%-10% of mutations in BRCA genes are associated with familial breast tumours in Eastern countries, suggesting the contribution of other genes. Using a microarray gen...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , |
| منشور في: |
2020
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| _version_ | 1864513549633585152 |
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| author | Balsam Rizeq (14779402) |
| author2 | Saïd Sif (13616740) Gheyath K. Nasrallah (9200525) Allal Ouhtit (526) |
| author2_role | author author author |
| author_facet | Balsam Rizeq (14779402) Saïd Sif (13616740) Gheyath K. Nasrallah (9200525) Allal Ouhtit (526) |
| author_role | author |
| dc.creator.none.fl_str_mv | Balsam Rizeq (14779402) Saïd Sif (13616740) Gheyath K. Nasrallah (9200525) Allal Ouhtit (526) |
| dc.date.none.fl_str_mv | 2020-09-05T18:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1111/jcmm.15761 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Novel_role_of_BRCA1_interacting_C_terminal_helicase_1_i_BRIP1_i_in_breast_tumour_cell_invasion/22258546 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Oncology and carcinogenesis Breast cancer (BC) BRIP1 Gene expression profiling Microarray Tumor progression Biomarkers |
| dc.title.none.fl_str_mv | Novel role of BRCA1 interacting C‐terminal helicase 1 (<i>BRIP1</i>) in breast tumour cell invasion |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Breast cancer (BC) is the most common malignancy and the leading cause of death in women worldwide. Only 5%-10% of mutations in BRCA genes are associated with familial breast tumours in Eastern countries, suggesting the contribution of other genes. Using a microarray gene expression profiling study of BC, we have recently identified <i>BRIP1</i> (fivefold up-regulation) as a potential gene associated with BC progression in the Omani population. Although <i>BRIP1</i> regulates DNA repair and cell proliferation, the precise role of <i>BRIP1</i> in BC cell invasion/metastasis has not been explored yet; this prompted us to test the hypothesis that <i>BRIP1</i> promotes BC cell proliferation and invasion. Using a combination of cellular and molecular approaches, our results revealed differential overexpression of <i>BRIP1</i> in different BC cell lines. Functional assays validated further the physiological relevance of <i>BRIP1</i> in tumour malignancy, and siRNA-mediated <i>BRIP1</i> knockdown significantly reduced BC cell motility by targeting key motility-associated genes. Moreover, down-regulation of <i>BRIP1</i> expression significantly attenuated cell proliferation via cell cycle arrest. Our study is the first to show the novel function of <i>BRIP1</i> in promoting BC cell invasion by regulating expression of various downstream target genes. Furthermore, these findings provide us with a unique opportunity to identify <i>BRIP1</i>-induced pro-invasive genes that could serve as biomarkers and/or targets to guide the design of appropriate BC targeted therapies.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Cellular and Molecular Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1111/jcmm.15761" target="_blank">http://dx.doi.org/10.1111/jcmm.15761</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_2994df7016214785e79620445b9ba891 |
| identifier_str_mv | 10.1111/jcmm.15761 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/22258546 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Novel role of BRCA1 interacting C‐terminal helicase 1 (<i>BRIP1</i>) in breast tumour cell invasionBalsam Rizeq (14779402)Saïd Sif (13616740)Gheyath K. Nasrallah (9200525)Allal Ouhtit (526)Biomedical and clinical sciencesOncology and carcinogenesisBreast cancer (BC)BRIP1Gene expression profilingMicroarrayTumor progressionBiomarkers<p dir="ltr">Breast cancer (BC) is the most common malignancy and the leading cause of death in women worldwide. Only 5%-10% of mutations in BRCA genes are associated with familial breast tumours in Eastern countries, suggesting the contribution of other genes. Using a microarray gene expression profiling study of BC, we have recently identified <i>BRIP1</i> (fivefold up-regulation) as a potential gene associated with BC progression in the Omani population. Although <i>BRIP1</i> regulates DNA repair and cell proliferation, the precise role of <i>BRIP1</i> in BC cell invasion/metastasis has not been explored yet; this prompted us to test the hypothesis that <i>BRIP1</i> promotes BC cell proliferation and invasion. Using a combination of cellular and molecular approaches, our results revealed differential overexpression of <i>BRIP1</i> in different BC cell lines. Functional assays validated further the physiological relevance of <i>BRIP1</i> in tumour malignancy, and siRNA-mediated <i>BRIP1</i> knockdown significantly reduced BC cell motility by targeting key motility-associated genes. Moreover, down-regulation of <i>BRIP1</i> expression significantly attenuated cell proliferation via cell cycle arrest. Our study is the first to show the novel function of <i>BRIP1</i> in promoting BC cell invasion by regulating expression of various downstream target genes. Furthermore, these findings provide us with a unique opportunity to identify <i>BRIP1</i>-induced pro-invasive genes that could serve as biomarkers and/or targets to guide the design of appropriate BC targeted therapies.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Cellular and Molecular Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1111/jcmm.15761" target="_blank">http://dx.doi.org/10.1111/jcmm.15761</a></p>2020-09-05T18:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1111/jcmm.15761https://figshare.com/articles/journal_contribution/Novel_role_of_BRCA1_interacting_C_terminal_helicase_1_i_BRIP1_i_in_breast_tumour_cell_invasion/22258546CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/222585462020-09-05T18:00:00Z |
| spellingShingle | Novel role of BRCA1 interacting C‐terminal helicase 1 (<i>BRIP1</i>) in breast tumour cell invasion Balsam Rizeq (14779402) Biomedical and clinical sciences Oncology and carcinogenesis Breast cancer (BC) BRIP1 Gene expression profiling Microarray Tumor progression Biomarkers |
| status_str | publishedVersion |
| title | Novel role of BRCA1 interacting C‐terminal helicase 1 (<i>BRIP1</i>) in breast tumour cell invasion |
| title_full | Novel role of BRCA1 interacting C‐terminal helicase 1 (<i>BRIP1</i>) in breast tumour cell invasion |
| title_fullStr | Novel role of BRCA1 interacting C‐terminal helicase 1 (<i>BRIP1</i>) in breast tumour cell invasion |
| title_full_unstemmed | Novel role of BRCA1 interacting C‐terminal helicase 1 (<i>BRIP1</i>) in breast tumour cell invasion |
| title_short | Novel role of BRCA1 interacting C‐terminal helicase 1 (<i>BRIP1</i>) in breast tumour cell invasion |
| title_sort | Novel role of BRCA1 interacting C‐terminal helicase 1 (<i>BRIP1</i>) in breast tumour cell invasion |
| topic | Biomedical and clinical sciences Oncology and carcinogenesis Breast cancer (BC) BRIP1 Gene expression profiling Microarray Tumor progression Biomarkers |