The miRNA<i>bantam</i>regulates growth and tumorigenesis by repressing the cell cycle regulator<i>tribbles</i>

Abstract

One of the fundamental issues in biology is understanding how organ size is controlled. Tissue growth has to be carefully regulated to generate well-functioning organs, and defects in growth control can result in tumor formation. The Hippo signaling pathway is a universal growth regulator and has been implicated in cancer. In <i>Drosophila</i>, the Hippo pathway acts through the miRNA <i>bantam</i> to regulate cell proliferation and apoptosis. Even though the <i>bantam</i> targets regulating apoptosis have been determined, the target genes controlling proliferation have not been identified thus far. In this study, we identify the gene <i>tribbles</i> as a direct <i>bantam</i> target gene. Tribbles limits cell proliferation by suppressing G2/M transition. We show that <i>tribbles</i> regulation by <i>bantam</i> is central in controlling tissue growth and tumorigenesis. We expand our study to other cell cycle regulators and show that deregulated G2/M transition can collaborate with oncogene activation driving tumor formation.