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...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Balsam Rizeq (14779402) (author)
مؤلفون آخرون: Saïd Sif (13616740) (author), Gheyath K. Nasrallah (9200525) (author), Allal Ouhtit (526) (author)
منشور في: 2020
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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
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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