Abstract
Receptor protein tyrosine phosphatase alpha (RPTPα), an activator of Src family kinases, is found significantly overexpressed in human cancer tissues. However, little is known about the regulation of RPTPα expression. miRNAs target multiple genes and play important roles in many cancer processes. Here, we identified a miRNA, miR-218 that binds directly to the 3'-UTR of RPTPα. Ectopic overexpression of miR-218 decreased RPTPα protein leading to decreased dephosphorylation of c-Src and decreased tumour growth in vitro and in vivo. A feedback loop between c-Src and miR-218 was revealed where c-Src inhibits transcription of SLIT2, which intronically hosts miR-218. These results show a novel regulatory pathway for RPTPα-c-Src signalling.
Keywords:
RPTPα; SLIT2; c-Src; miR-218; tumorigenesis.
© 2015 FEBS.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions
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Animals
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Binding Sites
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CSK Tyrosine-Protein Kinase
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Cell Movement
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Feedback, Physiological
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Gene Expression Regulation
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Humans
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism
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Lung Neoplasms / genetics
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Lung Neoplasms / pathology
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Male
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Mice, Inbred BALB C
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MicroRNAs / metabolism*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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RNA, Messenger / metabolism
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Receptor-Like Protein Tyrosine Phosphatases, Class 4 / genetics
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Receptor-Like Protein Tyrosine Phosphatases, Class 4 / metabolism*
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Signal Transduction / genetics
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Xenograft Model Antitumor Assays
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src-Family Kinases / genetics
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src-Family Kinases / metabolism*
Substances
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3' Untranslated Regions
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Intercellular Signaling Peptides and Proteins
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MIRN128 microRNA, human
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MicroRNAs
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Nerve Tissue Proteins
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RNA, Messenger
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CSK Tyrosine-Protein Kinase
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src-Family Kinases
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CSK protein, human
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PTPRA protein, human
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Receptor-Like Protein Tyrosine Phosphatases, Class 4
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Slit homolog 2 protein