miR-100 and miR-125b Contribute to Enhanced 3D Growth and Invasiveness and can be Functionally Transferred to Silence Target Genes in Recipient Cells

Extracellular communication via the transfer of vesicles and nanoparticles is now recognized to play an important role in tumor microenvironment interactions. Colorectal cancer (CRC) cells upregulate and secrete abundant levels of miR-100 and miR-125b that can alter gene expression by cell- and non-cell-autonomous mechanisms. We previously showed that these miRNAs activate Wnt signaling through noncanonical pairing with 5 negative regulators of Wnt signaling. To identify additional targets of miR-100 and miR-125b, we used bioinformatic approaches comparing multiple CRC cell lines, including knockout lines lacking one or both miRNAs. From an initial list of 96 potential mRNA targets, we tested 15 targets with 8 showing significant downregulation in the presence of miR-100 and miR-125b. Among these, Cingulin (CGN) and Protein tyrosine phosphatase receptor type-R (PTPRR) are downregulated in multiple cancers, consistent with regulation by increased levels of miR-100 and miR-125b. We also show that increased levels of miR-100 and miR-125b enhance 3D growth and invasiveness. Lastly, we show that miR-100 and miR-125b can be functionally transferred between cells to silence both reporter and endogenous mRNA targets. ### Competing Interest Statement The authors have declared no competing interest.