Abstract
MicroRNAs (miRNAs) are essential for regulating normal embryonic development and carcinogenesis. Here we report that miR-17-5p, an oncofoetal miRNA, is a key regulator of colorectal cancer progression. We show that miR-17-5p is an oncogenic miRNA that regulates tumorigenesis and progression by targeting the gene encoding P130 and subsequently activating the Wnt/β-catenin pathway. Using specimens from two large cohorts of colorectal cancer patients, we found that patients whose tumours had high miR-17-5p expression had shorter overall survival rates but showed a better response to adjuvant chemotherapy than did patients whose tumours had low miRNA expression. We also observed a strong inverse correlation between miR-17-5p and P130 expression. The current findings suggest that miR-17-5p is a crucial determinant of colorectal cancer progression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / physiology
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Cell Line, Tumor
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Colorectal Neoplasms / diagnosis
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Colorectal Neoplasms / genetics*
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Colorectal Neoplasms / mortality
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Colorectal Neoplasms / physiopathology
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Crk-Associated Substrate Protein / antagonists & inhibitors*
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Crk-Associated Substrate Protein / biosynthesis
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Down-Regulation / genetics
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic / genetics
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Gene Expression Regulation, Neoplastic / physiology
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Humans
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Mice
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Mice, Inbred BALB C
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MicroRNAs / biosynthesis
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MicroRNAs / physiology*
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / physiopathology
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Prognosis
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Real-Time Polymerase Chain Reaction
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Survival Analysis
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Wnt Signaling Pathway / physiology
Substances
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Crk-Associated Substrate Protein
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MIRN17 microRNA, human
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MicroRNAs