Impact of Microenvironmental Stress on miRNA Expression and Invasive Properties in Cultured Breast Cancer Cells

The relationship between miRNA expression and the onset, development, and advancement of aggressive cancers keeps miRNAs a subject of keen interest, and is the primary focus of this study. miRNAs are known to play critical roles as both proto-oncogene and tumor suppressor gene products. We are hypothesizing that stresses imposed within the tumor microenvironment of a cancer cell may become overly harsh, creating unsuitable conditions and provoking a cellular response that impacts expression levels for select miRNAs, and ultimately, the cancer cell’s invasiveness. In this study, we explore how stresses affect levels of expression for miR-145 and miR-330-3p in MCF7, MB-468, and MB-231 breast cancer cell lines, and we examine the effects of these altered miRNA expression levels on the invasiveness of MCF7 and MB468 cells. miR-145 is a tumor suppressor found to be down regulated in breast cancers. Its regulatory actions and targets can be associated with a number of critical cellular pathways. In contrast, miRNA-330-3p is a protooncogene product found to be overexpressed in breast cancers. We expected to find lowered levels of miR-145 expression and increased levels of miR-330-3p expression in breast cancer cells exposed to stress, compared with breast cancer cells grown in normal conditions. We also expected MCF7 and MB468 cells exposed to stress would prove to be more invasive than those grown in normal conditions. Although mixed results are reported, some data collected for this study appear to support our hypothesis. miRNA expression data in agreement with this hypothesis include down-regulation of miR-145 in cells exposed to dual stress conditions, as well as upregulation of miR-330-3p in cells exposed to hypoxic stress (for all 3 cell lines), and in MCF7 and MB231 cells exposed to heat stress. Some invasion data in agreement with our hypothesis are also reported. Cell migration increased among MCF7 cells exposed to hypoxic stress, and a marked increase in cell migration was observed for MB468 cells under all stress conditions, compared with those under normal conditions. These data are all in agreement with our hypothesis, suggesting that stress conditions in the tumor microenvironment could be a trigger for metastatic cell behavior.Master of Science (MS)BiologyUniversity of Michigan-Flinthttp://deepblue.lib.umich.edu/bitstream/2027.42/169164/1/Kaaykati2021.pdfDescription of Kaaykati2021.pdf : thesi