Abstract
Down-regulation of let-7 microRNA (miRNA) is a key event in lung cancer. Despite recent advances in survival signaling, the roles of let-7 in the context of lung cancer are not fully clear. In this study, we showed that let-7a, a member of let-7 family, negatively regulated the expression of NIRF through NIRF 3' UTR. We also showed that NIRF was required for the let-7a-mediated elevation of p21(WAF1). These findings suggest that growth-inhibitory effect of let-7a on the A549 cells in vitro and in vivo may be explained in part by le-7a-induced suppression of NIRF and elevation of p21(WAF1). This work reveals a novel regulatory mechanism for let-7a in the control of cellular proliferation and lung carcinogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions / genetics
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Animals
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Base Sequence
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Binding Sites
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Cell Line, Tumor
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Cell Proliferation
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Cell Transformation, Neoplastic
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Computational Biology
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Conserved Sequence
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
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Down-Regulation / genetics
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Gene Expression Regulation, Neoplastic / genetics*
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Humans
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Lung Neoplasms / genetics
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Lung Neoplasms / pathology*
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Mice
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Mice, Inbred BALB C
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Phylogeny
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Ubiquitin-Protein Ligases / genetics*
Substances
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3' Untranslated Regions
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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MicroRNAs
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mirnlet7 microRNA, human
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UHRF2 protein, human
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Ubiquitin-Protein Ligases