Abstract 4174: miR-17-92 as a therapeutic target in gastric cancer.

Abstract

Abstract We previously reported that 82 gastric cancer patients overexpress miR-17-5p, compared with healthy volunteers [median tumor/normal ratio, 1.6; false discovery rate<0.001]. Although 13q31.3 amplification has been reported in gastric cancer, the exact frequency of MIR17HG gene amplification in gastric cancer has not been systematically investigated. Using combined CGH and expression array analyses, we identified genomic abnormalities associated with miR-17-5p expression. No copy number alteration of MIR17HG was identified among the 32 study patients. Median or higher levels of miR-17-5p expression in gastric cancer patients were associated with copy number gain and overexpression of known oncogenes such as MYC and FGFR2. Based on mRNA expression microarray, genes differentially expressed between the high miR-17-expressing tumors and healthy volunteers were significantly enriched in MYC target genes (LS P value, 0.007). MYC knockdown in SNU-16 gastric cancer cells significantly decreased miR-17-92 expression. Although transcriptional activation, rather than gene amplification, was identified as the primary mechanism underlying miR-17-92 overexpression in gastric cancer, miR-17-5p inhibition led to suppressed monolayer and anchorage-independent growth and increased G1/S phase ratio in KATO-III cells which harbor FGFR2 gene amplification. Hence, miR-17-92 may serve as a therapeutic target in gastric cancer (supported by the Proteogenomic Research Program through the National Research Foundation of Korea funded by the Korean Ministry of Education, Science and Technology; and by Korean National Cancer Center Grant 121005). Citation Format: Dong M. park, Seok C. Lee, Hark K. Kim. miR-17-92 as a therapeutic target in gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4174. doi:10.1158/1538-7445.AM2013-4174