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• W2106532933 abstract "Despite their potential to regulate approximately one-third of the whole genome, relatively few microRNA (miRNA) targets have been experimentally validated, particularly in stratified squamous epithelia. Here we demonstrate not only that the lipid phosphatase SHIP2 is a target of miRNA-205 (miR-205) in epithelial cells, but, more importantly, that the corneal epithelial-specific miR-184 can interfere with the ability of miR-205 to suppress SHIP2 levels. This is the first example of a miRNA negatively regulating another to maintain levels of a target protein. Interfering with miR-205 function by using a synthetic antagomir, or by the ectopic expression of miR-184, leads to a coordinated damping of the Akt signaling pathway via SHIP2 induction. This was associated with a marked increase in keratinocyte apoptosis and cell death. Aggressive squamous cell carcinoma (SCC) cells exhibited elevated levels of miR-205. This was associated with a concomitant reduction in SHIP2 levels. Partial knockdown of endogenous miR-205 in SCCs markedly decreased phosphorylated Akt and phosphorylated BAD levels and increased apoptosis. We were able to increase SHIP2 levels in SCC cells after inhibition of miR-205. Therefore, miR-205 might have diagnostic value in determining the aggressivity of SCCs. Blockage of miR-205 activity with an antagomir or via ectopic expression of miR-184 could be novel therapeutic approaches for treating aggressive SCCs." @default.
• W2106532933 created "2016-06-24" @default.
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• W2106532933 date "2008-12-09" @default.
• W2106532933 modified "2023-10-03" @default.
• W2106532933 title "MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia" @default.
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• W2106532933 doi "https://doi.org/10.1073/pnas.0803992105" @default.
• W2106532933 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2587229" @default.
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• W2106532933 hasPublicationYear "2008" @default.
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