Seminar

Role of miRs in human breast cancer stem cells

Prof. Gerolama Condorelli

Breast cancer remains one of the leading causes of cancer mortality among women. Evidence suggest that the onset of cancer depends on a small population of cells, the cancer stem cells (CSC), that possess self-renewal and multilineage differentiation potential as well as a robust ability to sustain tumorigenesis. CSCs contribute to chemotherapy resistance, survival under hypoxic conditions and metastatic process. However, the molecular pathways underlying CSC biology are not yet well characterized. MicroRNAs (miRs) are small noncoding RNAs that act as negative regulator of gene expression, and have emerged as critical players in the maintenance of self-renewal in normal and cancer stem cells. Considering the central role of the CSCs in breast cancer development, we decided to study the functional role of miRs in the regulation breast cancer stem cells (BCSCs) phenotype. We found that miR-221 and miR-24 are upregulated in BCSCs, and that their overexpression increases the number of mammospheres and the expression of stem cell markers. Interestingly, we found that miR-221 upregulates stemness genes, such as Nanog and Oct 3/4, through the downregulation of the DNA Methyltransferase, DNMT3b. On the other hand, miR-24 induces apoptosis resistance through the regulation of BimL expression. In conclusion, miR-221 and 24 regulate critical aspects of CSCs biology such as self-renewal, chemoresistance and hypoxia survival, contributing to breast cancer tumorigenicity.