title: miR-8 modulates cytoskeletal regulators to influence cell survival and epithelial organization in Drosophila wings.
abstract: The miR-200 microRNA family plays important tumor suppressive roles. The sole Drosophila miR-200 ortholog, miR-8 plays conserved roles in Wingless, Notch and Insulin signaling - pathways linked to tumorigenesis, yet homozygous null animals are viable and often appear morphologically normal. We observed that wing tissues mosaic for miR-8 levels by genetic loss or gain of function exhibited patterns of cell death consistent with a role for miR-8 in modulating cell survival in vivo. Here we show that miR-8 levels impact several actin cytoskeletal regulators that can affect cell survival and epithelial organization. We show that loss of miR-8 can confer resistance to apoptosis independent of an epithelial to mesenchymal transition while the persistence of cells expressing high levels of miR-8 in the wing epithelium leads to increased JNK signaling, aberrant expression of extracellular matrix remodeling proteins and disruption of proper wing epithelial organization. Altogether our results suggest that very low as well as very high levels of miR-8 can contribute to hallmarks associated with cancer, suggesting approaches to increase miR-200 microRNAs in cancer treatment should be moderate.
authors.affiliation: University of Michigan, Department of Molecular, Cellular and Developmental Biology, Ann Arbor, MI 48109, United States.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Bolin
authors.affiliation: University of Michigan, Department of Molecular, Cellular and Developmental Biology, Ann Arbor, MI 48109, United States.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Rachmaninoff
authors.affiliation: Vassar College, Department of Biology, Poughkeepsie, NY 12604, United States.
authors.forename: Kea
authors.initials: K
authors.lastname: Moncada
authors.affiliation: Vassar College, Department of Biology, Poughkeepsie, NY 12604, United States.
authors.forename: Katharine
authors.initials: K
authors.lastname: Pula
authors.affiliation: Vassar College, Department of Biology, Poughkeepsie, NY 12604, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kennell
authors.affiliation: University of Michigan, Department of Molecular, Cellular and Developmental Biology, Ann Arbor, MI 48109, United States. Electronic address: buttitta@umich.edu.
authors.forename: Laura
authors.initials: L
authors.lastname: Buttitta
mesh_terms: D000818:Animals; D003599:Cytoskeleton / Q000502:physiology*; D004330:Drosophila / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D014921:Wings, Animal / Q000254:growth & development*
chemical_list: D035683:MicroRNAs
keywords: Actin cytoskeleton; Drosophila; Imaginal wing disc; miRNA