The Study of Differentially Expressed MicroRNAs in Breast Cancer Cells Through Interaction with Endothelial Cells

Breast cancer is the most common cancer worldwide and the main cause of death among women. This disease is highly complex and heterogeneous which affects the diagnosis and treatment of the disease. The interaction between breast cancer cells and their tumor microenvironment is very essential for breast cancer development. There are many types of cells that constitute the tumor microenvironment such as fibroblasts, endothelial cells, pericytes, immune cells and extracellular matrix. Out of these cells, the most crucial cell type to the survival of breast cancer cells and is involved in angiogenesis is the endothelial cells. MicroRNAs(miRNAs) are small non-coding RNAs that play a crucial role in many biological processes such as cell proliferation, differentiation and apoptosis by regulating gene expression. Recent studies have demonstrated that interaction between Breast cancer and Endothelial cells changes the gene expression. Consequently, we hypothesized that the interaction between breast cancer and endothelial cells can modulate the expression of miRNAs in breast cancer cells which in turn modulate the biology of breast cancer. By co-culturing breast cancer cell line MDA-MB231 with endothelial cells and analyzing the differentially expressed miRNAs in both cell types, we observed that miR-146a was exclusively downregulated in co-cultured breast cancer cells which was identified previously to be a tumor suppressor. We detected miR-589 was upregulated in co-cultured breast cancer cells and downregulated in ECs. MiR-18a was upregulated in both cell types, however, it was reported to be downregulated in metastatic breast cancer cells. These miRNA signatures observed in breast cancer cells indicate that interaction between epithelial and stromal compartments of breast cancer may play a role in breast cancer progression which could be a novel target for treatment.