Abstract
Emerging research has suggested that miRNAs play a significant role in oncogenesis and tumor progression by regulating multiple molecular pathways. Here, we investigated miR-300, which inhibited bladder cancer (BCa) migration by regulating the SP1/MMP9 pathway. miR-300, belonging to the DLK1-DIO3 miRNA cluster, is frequently expressed at lower levels in BCa tissue than in adjacent normal tissue due to DNA methylation. Reinforced expression of miR-300 significantly suppressed the migration of BCa cells. We carried out a search of online databases to predict potential targets of miR-300. Further studies determined that miR-300 directly targeted SP1 and suppressed its expression by specifically binding to its 3'-untranslated region. Meanwhile, downregulated MMP9 may be the final effector of BCa cell mobility. Small interference RNAs silencing SP1 phenocopied the effects of miR-300 overexpression, while restoration of SP1 expression partially rescued the inhibition of metastasis induced by miR-300 overexpression in BCa cells. In conclusion, we unveiled a miR-300/SP1/MMP9 pathway in BCa. These findings demonstrate that miR-300 is a promising tumor suppressor in BCa.
Keywords:
matrix metalloproteinase; miRNA; migration.
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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Antagomirs / metabolism
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Calcium-Binding Proteins
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Cell Line, Tumor
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Cell Movement
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Humans
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Intercellular Signaling Peptides and Proteins / chemistry*
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Intercellular Signaling Peptides and Proteins / metabolism
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Kaplan-Meier Estimate
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Matrix Metalloproteinase 9 / metabolism*
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Membrane Proteins / chemistry*
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Membrane Proteins / metabolism
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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RNA Interference
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RNA, Small Interfering / metabolism
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Sp1 Transcription Factor / antagonists & inhibitors
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Sp1 Transcription Factor / genetics
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Sp1 Transcription Factor / metabolism*
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Urinary Bladder Neoplasms / metabolism
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Urinary Bladder Neoplasms / mortality
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Urinary Bladder Neoplasms / pathology*
Substances
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3' Untranslated Regions
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Antagomirs
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Calcium-Binding Proteins
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DLK1 protein, human
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Intercellular Signaling Peptides and Proteins
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MIRN300 microRNA, human
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Membrane Proteins
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MicroRNAs
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RNA, Small Interfering
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Sp1 Transcription Factor
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MMP9 protein, human
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Matrix Metalloproteinase 9
Grants and funding
This work was supported by grants from the National Natural Science Foundation of China (grant no. 81472375 and no. 81702500) and the Natural Science Foundation of Zhejiang Province (LQ16H160011).