Functional Transfer of miRNA Promotes Cancer Cell Growth and Enhances Invasiveness

Abstract

microRNAs display increased expression in cells and extracellular vesicles and nanoparticles (EVPs) from cancer cells. miR-100 and miR-125b were previously identified as having increased expression in colorectal cancer cells. Utilizing a combination of bioinformatics and analysis of gene expression patterns in both wild type and miR-100/miR-125b colorectal cancer cell lines, 96 different potential miR-100 and miR-125b targets were identified and 13 were verified as targets by reporter assays. Among those targets, I found that one of the most statistically downregulated proteins in these assays was Cingulin (CGN), a protein that links the cytoskeleton to tight junctions. I found that increased expression of miR-100 and miR-125b causes cell-autonomous downregulation of CGN and that transfer of miR-100 and miR-125b by extracellular vesicles can inhibit CGN expression in recipient cells in a non-cell-autonomous manner. Consistent with a role for tight junctions in invasion and metastasis of colorectal cancer cells, I found that downregulation of CGN by miR-100 and miR-125b increased 3D growth and invasiveness in both colorectal and glioblastoma cancer cell lines.