| MicroRNA-130b regulates the tumour suppressor RUNX3 in gastric cancer. | |
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MedLine Citation:
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PMID: 20176475 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIM: Accumulating evidence indicates that RUNX3 is an important tumour suppressor that is inactivated in many cancer types. This study aimed to assess the role of microRNA (miRNA) in the regulation of RUNX3. METHODS: Four bioinformatic algorithms were used to predict miRNA binding to RUNX3. The correlation between candidate miRNAs and RUNX3 expression in cell lines was determined by real-time reverse transcriptase quantitative PCR (RT-qPCR) and Western blot. Candidate miRNAs were tested for functional effects through transfection of miRNA precursors and inhibitors, and monitoring cell viability, apoptosis and Bim expression. miRNA and RUNX3 expression, RUNX3 methylation and RUNX3 protein levels were assessed in gastric tissue by RT-qPCR, Methylight analysis and immunohistochemistry, respectively. RESULTS: Bioinformatics, gene and protein expression analysis in eight gastric cell lines identified miR-130b as the top candidate miRNA for RUNX3 binding. Overexpression of miR-130b increased cell viability, reduced cell death and decreased expression of Bim in TGF-beta mediated apoptosis, subsequent to the downregulation of RUNX3 protein expression. In 15 gastric tumours, miR-130b expression was significantly higher compared to matched normal tissue, and was inversely associated with RUNX3 hypermethylation. CONCLUSION: Attenuation of RUNX3 protein levels by miRNA may reduce the growth suppressive potential of RUNX3 and contribute to tumourigenesis. |
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Authors:
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Kin Wai Lai; King Xin Koh; Marie Loh; Kotaro Tada; Manish Mani Subramaniam; Xn Yii Lim; Aparna Vaithilingam; Manuel Salto-Tellez; Barry Iacopetta; Yoshiaki Ito; Richie Soong; |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-20 |
Journal Detail:
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Title: European journal of cancer (Oxford, England : 1990) Volume: 46 ISSN: 1879-0852 ISO Abbreviation: Eur. J. Cancer Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-03 Completed Date: 2010-09-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9005373 Medline TA: Eur J Cancer Country: England |
Other Details:
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Languages: eng Pagination: 1456-63 Citation Subset: IM |
Copyright Information:
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Crown Copyright (c) 2010. Published by Elsevier Ltd. All rights reserved. |
Affiliation:
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Cancer Science Institute of Singapore, Centre for Life Sciences #02-15, 28 Medical Drive, National University of Singapore, Singapore 117456, Singapore. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Algorithms Cell Line, Tumor Core Binding Factor Alpha 3 Subunit / genetics, metabolism* Down-Regulation / physiology Gene Expression Regulation, Neoplastic / drug effects, genetics* Genes, Tumor Suppressor* Humans Immunohistochemistry MicroRNAs / metabolism* Stomach Neoplasms / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Core Binding Factor Alpha 3 Subunit; 0/MicroRNAs; 0/Runx3 protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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