Oncogenic cooperation between Yorkie and the conserved microRNA<i>miR-8</i>in the wing disc of<i>Drosophila</i>

Abstract

Tissue growth has to be carefully controlled to generate well-functioning organs. MicroRNAs are small non-coding RNAs that modulate the activity of target genes and play a pivotal role in animal development. Understanding the functions of microRNAs in development requires the identification of their target genes. Here, we find that <i>miR-8</i>, a conserved microRNA in the <i>miR-200</i> family, controls tissue growth and homeostasis in the <i>Drosophila</i> wing imaginal disc. Upregulation of <i>miR-8</i> causes the repression of <i>Yorkie</i>, the effector of the Hippo pathway in <i>Drosophila</i>, and reduces tissue size. Remarkably, co-expression of <i>Yorkie</i> and <i>miR-8</i> causes the formation of neoplastic tumors. We show that upregulation of <i>miR-8</i> represses the growth inhibitor <i>brinker</i>, and depletion of <i>brinker</i> cooperates with <i>Yorkie</i> in the formation of neoplastic tumors. Hence, <i>miR-8</i> modulates a positive growth regulator, <i>Yorkie</i>, and a negative growth regulator, <i>brinker</i> Deregulation of this network can result in the loss of tissue homeostasis and the formation of tumors.