| Experiment ID | EXP00131 |
| Reference | Title: Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptoticfactor in gastric cancer. Author: Oh HK, Tan AL, Das K, Ooi CH, Deng NT, Tan IB, Beillard E, Lee J, RamnarayananK, Rha SY, Palanisamy N, Voorhoeve PM, Tan P. Journal: Clin Cancer Res. 2011 May 1;17(9):2657-67. doi: 10.1158/1078-0432.CCR-10-3152.Epub 2011 Mar 17. Abstract: PURPOSE: MicroRNAs (miRNA) play pivotal oncogenic and tumor-suppressor roles inseveral human cancers. We sought to discover novel tumor-suppressor miRNAs ingastric cancer (GC).EXPERIMENTAL DESIGN: Using Agilent miRNA microarrays, we compared miRNAexpression profiles of 40 primary gastric tumors and 40 gastric normal tissues,identifying miRNAs significantly downregulated in gastric tumors.RESULTS: Among the top 80 miRNAs differentially expressed between gastric tumors and normals (false discovery rate < 0.01), we identified hsa-miR-486 (miR-486) asa significantly downregulated miRNA in primary GCs and GC cell lines. Restorationof miR-486 expression in GC cell lines (YCC3, SCH and AGS) caused suppression of several pro-oncogenic traits, whereas conversely inhibiting miR-486 expression inYCC6 GC cells enhanced cellular proliferation. Array-CGH analysis of 106 primary GCs revealed genomic loss of the miR-486 locus in approximately 25% to 30% ofGCs, including two tumors with focal genomic losses specifically deletingmiR-486, consistent with miR-486 playing a tumor-suppressive role. Bioinformatic analysis identified the secreted antiapoptotic glycoprotein OLFM4 as a potential miR-486 target. Restoring miR-486 expression in GC cells decreased endogenousOLFM4 transcript and protein levels, and also inhibited expression of luciferase reporters containing an OLFM4 3' untranslated region with predicted miR-486binding sites. Supporting the biological relevance of OLFM4 as a miR-486 target, proliferation in GC cells was also significantly reduced by OLFM4 silencing.CONCLUSIONS: miR-486 may function as a novel tumor-suppressor miRNA in GC. Itsantioncogenic activity may involve the direct targeting and inhibition of OLFM4. PMID: 21415212 |
| Expressiion Profile | Description: miRNA expressions in non-cancerous and cancerous human gastric tissues Organism: Homo sapiens GEO ID: GSE23739 Platform: GPL7731 Number of samples: 80 |
| Design and Sample | Cancer Type: gastric cancer Cancer SubType: N/D Cell Line: N/D Experimental Design: cancer vs normal Case Sample: gastric cancer Control Sample: normal tissue Num of Case: 40 Num of Control: 40 Quantification Software: Limma Num of miRNAs: 719 |
| Identification | Num of Up: 111 Num of Down: 120 |