Abstract 2056: MicroRNA-126 inhibits SOX2 expression in gastric cancer cells

Abstract

Abstract A transcription factor SOX2 is essential for embryonic development and play critical roles in the maintenance of embryonic stem cell's pluripotency. We previously reported that SOX2 plays important roles in growth inhibition through cell cycle arrest and apoptosis, and SOX2 expression was frequently down-regulated in gastric cancers, some of which were due to aberrant DNA methylation. However, the mechanisms underlying loss of SOX2 expression and its target genes involved in gastric carcinogenesis remain largely unknown. In this study, we initially assessed whether microRNAs, small noncoding RNAs, control SOX2 expression in gastric cancers. In silico analysis revealed that microRNA-126 (miR-126) has two predictive target sites in the 3′-UTR of the SOX2 mRNA. Gain- and loss-of function experiments demonstrated that miR-126 inhibited SOX2 expression in gastric cancer cell lines. Luciferase reporter assays with a pGL4-SOX2 3′-UTR vector revealed that miR-126 directly inhibits SOX2 expression by targeting two binding sites in the 3′-UTR of the SOX2 mRNA independently. Some primary gastric cancer tissues with low expression of SOX2 exhibited markedly high levels of miR-126 expression compared with paired non-cancerous mucosae. To further understand the potential effects of miR-126-induced down-regulation of SOX2 on gastric carcinogenesis, we next attempted to identify the downstream target genes of SOX2 in gastric cancer cells. The microarray analysis after SOX2 over-expression in a gastric cancer cell line showed that 437 genes were up-regulated (>2-fold) and 447 genes were down-regulated (<0.5-fold), some of which were cancer-related genes. Taken together, we identified miR-126 as a novel microRNA which inhibits SOX2 expression in gastric cancer cells, and suggest that aberrant miR-126 expression and consequent SOX2 down-regulation may contribute to gastric carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2056.