Abstract
MicroRNAs (miRNAs) have been proposed as critical regulatory molecules in the epithelial-mesenchymal transition (EMT) program. However, the roles of mature miRNA biogenesis during EMT process needs to be defined. Here we determined that increased expression of XRN2 induced EMT and promoted metastasis in vitro and in vivo. Furthermore, we uncovered that XRN2 functions as pro-metastatic gene, which accelerates miR-10a maturation by binding pre-miR-10a in a DICER-independent manner. These findings suggest that XRN2 is a novel regulator of EMT that contributes to the metastatic processes in lung cancer through a novel miRNA regulatory mechanism.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carcinoma, Non-Small-Cell Lung / enzymology*
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Carcinoma, Non-Small-Cell Lung / mortality
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Carcinoma, Non-Small-Cell Lung / secondary
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Cell Line, Tumor
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Cell Movement
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DEAD-box RNA Helicases / metabolism
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Disease-Free Survival
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Epithelial-Mesenchymal Transition*
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Exoribonucleases / physiology*
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Kaplan-Meier Estimate
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Lung Neoplasms / enzymology*
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Lung Neoplasms / mortality
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Lung Neoplasms / pathology
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Mice, Inbred NOD
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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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Prognosis
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Proportional Hazards Models
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Protein Binding
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RNA Processing, Post-Transcriptional
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Ribonuclease III / metabolism
Substances
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MIRN10 microRNA, human
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MicroRNAs
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Exoribonucleases
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XRN2 protein, human
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DICER1 protein, human
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Ribonuclease III
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DEAD-box RNA Helicases