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Novel role of BRCA1 interacting C‐terminal helicase 1 (BRIP1) in breast tumour cell invasion
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2020
- Publisher :
- John Wiley and Sons Inc., 2020.
-
Abstract
- 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 BRIP1 (fivefold up‐regulation) as a potential gene associated with BC progression in the Omani population. Although BRIP1 regulates DNA repair and cell proliferation, the precise role of BRIP1 in BC cell invasion/metastasis has not been explored yet; this prompted us to test the hypothesis that BRIP1 promotes BC cell proliferation and invasion. Using a combination of cellular and molecular approaches, our results revealed differential overexpression of BRIP1 in different BC cell lines. Functional assays validated further the physiological relevance of BRIP1 in tumour malignancy, and siRNA‐mediated BRIP1 knockdown significantly reduced BC cell motility by targeting key motility‐associated genes. Moreover, down‐regulation of BRIP1 expression significantly attenuated cell proliferation via cell cycle arrest. Our study is the first to show the novel function of BRIP1 in promoting BC cell invasion by regulating expression of various downstream target genes. Furthermore, these findings provide us with a unique opportunity to identify BRIP1‐induced pro‐invasive genes that could serve as biomarkers and/or targets to guide the design of appropriate BC targeted therapies.
- Subjects :
- Wound Healing
proliferation
BRIP1
Down-Regulation
Breast Neoplasms
Original Articles
Cell Cycle Checkpoints
invasion
targeted therapy
Fanconi Anemia Complementation Group Proteins
Gene Expression Regulation, Neoplastic
breast cancer
Cell Movement
Cell Line, Tumor
metastasis
Humans
Original Article
Female
Neoplasm Invasiveness
RNA, Messenger
RNA, Small Interfering
RNA Helicases
Cell Proliferation
Subjects
Details
- Language :
- English
- ISSN :
- 15824934 and 15821838
- Volume :
- 24
- Issue :
- 19
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.pmid..........1579f45b08120d8d8c61c556d4466e29