Novel role of BRCA1 interacting C-terminal helicase 1 (BRIP1)in breast tumour cell invasion

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 identifiedBRIP1(fivefold up-regulation) as a potential gene associated with BC progression in the Omani population. AlthoughBRIP1regulates DNA repair and cell proliferation, the precise role ofBRIP1in BC cell invasion/metastasis has not been explored yet; this prompted us to test the hypothesis thatBRIP1promotes BC cell proliferation and invasion. Using a combination of cellular and molecular approaches, our results revealed differential overexpression ofBRIP1in different BC cell lines. Functional assays validated further the physiological relevance ofBRIP1in tumour malignancy, and siRNA-mediatedBRIP1knockdown significantly reduced BC cell motility by targeting key motility-associated genes. Moreover, down-regulation ofBRIP1expression significantly attenuated cell proliferation via cell cycle arrest. Our study is the first to show the novel function ofBRIP1in promoting BC cell invasion by regulating expression of various downstream target genes. Furthermore, these findings provide us with a unique opportunity to identifyBRIP1-induced pro-invasive genes that could serve as biomarkers and/or targets to guide the design of appropriate BC targeted therapies.