The Role of MicroRNAs Regulated Breast Cancer Stem Cells in the Pathogenesis, Prognosis and Aggressiveness of Breast Cancer

Abstract

Breast cancer is a leading cause of cancer related death among women worldwide and it is a complex disease characterized by its heterogeneity. The heterogenous characteristic of the breast cancer is responsible for its aggressiveness and treatment resistance. Breast cancer stem cells (BCSCs) are population of heterogenous cells with increased propensity for proliferation, differentiation, migration, invasion and mammosphere formation with increased resistance to treatment. They have ability to initiate and propagate cancer cells population and share similarity with the normal stem cells in relation to their expressions of cell surface markers; Cluster of Differentiation 44 positive (CD44+), Cluster of Differentiation 24 negative/low (CD24-/low) and Alkaline dehydrogenase 1 (ALDH1).
 MicroRNAs (miRNAs) are responsible for the RNA silencing and post-transcriptional regulation of the gene expression. MicroRNAs (miRNAs) control gene expression by acting as oncogenes or tumor suppressor genes. The epigenetic mechanisms are used for the regulation of miRNAs expression in the breast cancer, and this can be targeted to reverse the cancer progression. This review aims to provide an overview of the pathogenic mechanism of the microRNA’s expressions on the breast cancer stem cells in controlling the prognosis and aggressiveness of breast cancer disease. This is done by highlighting the regulatory mechanism of miRNA expressions on the BCSCs.
 Dysregulation of the MicroRNAs expression in the breast cancer stem cells and upregulated miRNAs expression were identified in the breast cancer stem cells (BCSCs), including miR-10b, miR-21, miR-155, miR-181, miR-183, miR-210 and miR-221/222, and the downregulated miRNAs expression in BCSCs include Let-7, miR-22, miR-30e, miR-31, miR-103/107, miR-200, miR-205, miR-335, miR-449a, miR-519c, miR-600, miR-708, miR-760. Studies showed association between the miRNA expression and breast cancer metastasis and aggressiveness. MicroRNAs were noticed to have a regulatory effect on neovascularization, drug resistance, and cancer metastasis. They can be used as predictive indicators in determining prognosis of breast cancer following cancer treatment and miRNAs expression can be used to determine the metastatic BCSCs for an efficient targeting mechanism and identification of the metastatic cancer cells. The systematic literature review aims at providing insight into the potential roles of microRNA in oncology especially breast cancers. The data for this study review were obtained from the Medline on OvidSP, includes PubMed of the US National Library of Medicine and the search was done through the University of Bristol Library services. This is to provide an overview of the pathogenic mechanism of microRNAs regulatory effect on the breast cancer stem cells in controlling the prognosis and aggressiveness of breast cancer disease. The review will be providing highlight of the dysregulation of oncogenic and tumor suppressor microRNAs in the breast cancer stem cells and highlighting the roles of miRNAs regulated BCSCs in the pathogenesis, prognosis, and aggressiveness of the breast cancer. We further discuss the biogenesis of miRNAs, regulatory roles of miRNAs on BCSCs, and then summarize the mechanism of miRNAs regulated BCSCs.