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

TY - JOUR

T1 - Oncogenic cooperation between Yorkie and the conserved microRNA miR-8 in the wing disc of Drosophila

AU - Sander, Moritz

AU - Eichenlaub, Teresa

AU - Herranz, Hećtor

PY - 2018

Y1 - 2018

N2 - 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 miR-8, a conserved microRNA in the miR-200 family, controls tissue growth and homeostasis in the Drosophila wing imaginal disc. Upregulation of miR-8 causes the repression of Yorkie, the effector of the Hippo pathway in Drosophila, and reduces tissue size. Remarkably, co-expression of Yorkie and miR-8 causes the formation of neoplastic tumors. We show that upregulation of miR-8 represses the growth inhibitor brinker, and depletion of brinker cooperates with Yorkie in the formation of neoplastic tumors. Hence, miR-8 modulates a positive growth regulator, Yorkie, and a negative growth regulator, brinker. Deregulation of this network can result in the loss of tissue homeostasis and the formation of tumors.

AB - 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 miR-8, a conserved microRNA in the miR-200 family, controls tissue growth and homeostasis in the Drosophila wing imaginal disc. Upregulation of miR-8 causes the repression of Yorkie, the effector of the Hippo pathway in Drosophila, and reduces tissue size. Remarkably, co-expression of Yorkie and miR-8 causes the formation of neoplastic tumors. We show that upregulation of miR-8 represses the growth inhibitor brinker, and depletion of brinker cooperates with Yorkie in the formation of neoplastic tumors. Hence, miR-8 modulates a positive growth regulator, Yorkie, and a negative growth regulator, brinker. Deregulation of this network can result in the loss of tissue homeostasis and the formation of tumors.

KW - Brinker

KW - Cancer

KW - Drosophila

KW - Hippo pathway

KW - MicroRNA

KW - miR-8

U2 - 10.1242/dev.153817

DO - 10.1242/dev.153817

M3 - Journal article

C2 - 29945869

AN - SCOPUS:85049881070

SN - 0950-1991

VL - 145

JO - Development

JF - Development

IS - 13

M1 - dev153817

ER -