UCLA

The activities of pathways that regulate malignant transformation can be influenced by microRNAs (miRs). Increased expression of tumor-suppressor miRs are associated with improved clinical outcomes in patients and reduced invasion of human cancer cell lines. In this thesis we investigate the mechanism underlying the reduced invasive potential of human ovarian cancer cells that are transfected with miR mimics representing five tumor-suppressor miRs (miR-508-3p, miR-508-5p, miR-509-3p, miR-509-5p, miR-130b-3p). Cells with elevated levels of tumor-suppressor miRs exhibit decreased invasion through collagen matrices, increased cell size, and reduced deformability as measured by microfiltration and microfluidic assays. To understand the molecular basis of altered invasion and deformability induced by these miRs, we use predicted and validated mRNA targets that encode structural and signaling proteins that regulate cell mechanical properties. Combined with image analysis of F-actin in single cells, our results suggest that these tumor-suppressor miRs may alter cell physical properties by regulating the actin cytoskeleton. Our findings provide biophysical insights into how tumor-suppressor miRs can regulate the invasive potential of ovarian cancer cells, and identify potential therapeutic targets that may be implicated in ovarian cancer progression.