Abstract
The LRIG1 [leucine-rich repeats and immunoglobulin-like domains (LRIG)] gene is not universally downregulated in human cancers, and its role in tumorigenesis and the development of glioma has not been well addressed. In this study, we used short hairpin RNA (shRNA)-triggered RNA interference (RNAi) to block LRIG1 gene expression in the GL15 human glioma cell line. Specific downregulation of LRIG1 by shRNA resulted in significantly enhanced capabilities of proliferation, inhibition of apoptosis and invasion in the GL15 cells. LRIG1 repression induced marked activation of epidermal growth factor receptor (EGFR), protein kinase B (Akt) and c-Myc signaling molecules. Our results demonstrated that RNAi against LRIG1 may effectively downregulate LRIG1 gene expression. LRIG1 functions as a tumor suppressor in the pathogenesis of glioma via EGFR/Akt/c-Myc activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis*
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Blotting, Western
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Brain Neoplasms / genetics
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Brain Neoplasms / metabolism
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Brain Neoplasms / pathology*
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Cell Adhesion
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Cell Movement
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Cell Proliferation
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ErbB Receptors / genetics
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ErbB Receptors / metabolism*
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Flow Cytometry
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Glioblastoma / genetics
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Glioblastoma / metabolism
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Glioblastoma / pathology*
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Humans
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Immunoprecipitation
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism*
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism*
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured
Substances
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LRIG1 protein, human
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MYC protein, human
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Membrane Glycoproteins
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Proto-Oncogene Proteins c-myc
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RNA, Messenger
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RNA, Small Interfering
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EGFR protein, human
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ErbB Receptors
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AKT1 protein, human
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Proto-Oncogene Proteins c-akt