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dc.contributor.authorDaniel, SG
dc.contributor.authorRuss, AD
dc.contributor.authorGuthridge, KM
dc.contributor.authorRaina, AI
dc.contributor.authorEstes, PS
dc.contributor.authorParsons, LM
dc.contributor.authorRichardson, HE
dc.contributor.authorSchroeder, JA
dc.contributor.authorZarnescu, DC
dc.date.accessioned2020-12-18T03:57:27Z
dc.date.available2020-12-18T03:57:27Z
dc.date.issued2018-01-01
dc.identifierpii: bio.027391
dc.identifier.citationDaniel, S. G., Russ, A. D., Guthridge, K. M., Raina, A. I., Estes, P. S., Parsons, L. M., Richardson, H. E., Schroeder, J. A. & Zarnescu, D. C. (2018). miR-9a mediates the role of Lethal giant larvae as an epithelial growth inhibitor in Drosophila. BIOLOGY OPEN, 7 (1), https://doi.org/10.1242/bio.027391.
dc.identifier.issn2046-6390
dc.identifier.urihttp://hdl.handle.net/11343/255993
dc.description.abstractDrosophila lethal giant larvae (lgl) encodes a conserved tumor suppressor with established roles in cell polarity, asymmetric division, and proliferation control. Lgl's human orthologs, HUGL1 and HUGL2, are altered in human cancers, however, its mechanistic role as a tumor suppressor remains poorly understood. Based on a previously established connection between Lgl and Fragile X protein (FMRP), a miRNA-associated translational regulator, we hypothesized that Lgl may exert its role as a tumor suppressor by interacting with the miRNA pathway. Consistent with this model, we found that lgl is a dominant modifier of Argonaute1 overexpression in the eye neuroepithelium. Using microarray profiling we identified a core set of ten miRNAs that are altered throughout tumorigenesis in Drosophila lgl mutants. Among these are several miRNAs previously linked to human cancers including miR-9a, which we found to be downregulated in lgl neuroepithelial tissues. To determine whether miR-9a can act as an effector of Lgl in vivo, we overexpressed it in the context of lgl knock-down by RNAi and found it able to reduce the overgrowth phenotype caused by Lgl loss in epithelia. Furthermore, cross-comparisons between miRNA and mRNA profiling in lgl mutant tissues and human breast cancer cells identified thrombospondin (tsp) as a common factor altered in both fly and human breast cancer tumorigenesis models. Our work provides the first evidence of a functional connection between Lgl and the miRNA pathway, demonstrates that miR-9a mediates Lgl's role in restricting epithelial proliferation, and provides novel insights into pathways controlled by Lgl during tumor progression.
dc.languageEnglish
dc.publisherCOMPANY BIOLOGISTS LTD
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titlemiR-9a mediates the role of Lethal giant larvae as an epithelial growth inhibitor in Drosophila
dc.typeJournal Article
dc.identifier.doi10.1242/bio.027391
melbourne.affiliation.departmentAnatomy and Neuroscience
melbourne.affiliation.departmentUniversity General
melbourne.source.titleBiology Open
melbourne.source.volume7
melbourne.source.issue1
melbourne.identifier.nhmrc299956
melbourne.identifier.nhmrc628401
dc.rights.licenseCC BY
melbourne.elementsid1299232
melbourne.contributor.authorGuthridge, Kathryn
melbourne.contributor.authorRichardson, Helena
melbourne.contributor.authorParsons, Linda
dc.identifier.eissn2046-6390
melbourne.identifier.fundernameidNHMRC, 299956
melbourne.identifier.fundernameidNHMRC, 628401
melbourne.accessrightsOpen Access


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