Abstract
We report that elevated microRNA-133b (miR-133b) acts as an oncogene in human cervical carcinoma to promote tumorigenesis and metastasis. In situ hybridization confirmed that miR-133b is localized in proliferating human cervical carcinoma cells with levels progressively elevating throughout advancing stages. Cellular studies showed that miR-133b enhances cell proliferation and colony formation by targeting mammalian sterile 20-like kinase 2 (MST2), cell division control protein 42 homolog (CDC42) and ras homolog gene family member A (RHOA), which subsequently results in activation of the tumorigenic protein kinase B alpha (AKT1) and mitogen-activated protein kinase (ERK1 and ERK2, here abbreviated as ERK) signaling pathways. Mouse experiments revealed that upregulation of miR-133b in cervical carcinoma cells strongly promotes both in vivo tumorigenesis and independent metastasis to the mouse lung. The data indicates that upregulation of miR-133b shortens the latency of cervical carcinoma. Together, these findings suggest that miR-133b could be a potent marker for the early onset of cervical carcinoma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Carcinoma / enzymology
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Carcinoma / genetics
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Carcinoma / metabolism
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Carcinoma / secondary
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Cell Line, Tumor
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Cell Proliferation
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism
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Cluster Analysis
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Female
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Gene Expression Regulation, Neoplastic*
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Humans
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MAP Kinase Signaling System*
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Mice
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Mice, SCID
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Neoplasm Transplantation
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins c-akt / metabolism*
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RNA Interference
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Serine-Threonine Kinase 3
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Transcription, Genetic
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Tumor Burden
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Uterine Cervical Neoplasms / enzymology
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Uterine Cervical Neoplasms / genetics
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Uterine Cervical Neoplasms / pathology
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cdc42 GTP-Binding Protein / genetics
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cdc42 GTP-Binding Protein / metabolism
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rhoA GTP-Binding Protein / genetics
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rhoA GTP-Binding Protein / metabolism
Substances
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MIRN133 microRNA, human
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MicroRNAs
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RHOA protein, human
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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STK3 protein, human
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Serine-Threonine Kinase 3
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cdc42 GTP-Binding Protein
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rhoA GTP-Binding Protein