Abstract 5338: MicroRNA-CGU promotes progression and metastasis through a negative regulation of ERM protein in human gastric cancer.

Abstract

Abstract Background: miRNAs have an important role in tumor carcinogenesis. They may act either as oncogenes or tumor suppressor genes through their regulated-target genes. The aim of this study was to identify useful biomarkers from miRNAs that might regulate the tumorigenesis or progression of gastric cancer. Materials and Methods: Differential miRNA profile was analyzed with a 270 miRNAs-based qRT-PCR assay in a total of 6 pairs of tumor tissues and matched non-tumor mucosa from surgical specimens. One of the top strongest up-regulated miRNAs was selected, and it was validated by qRT-PCR in fresh frozen tissues of gastrectomized specimens from gastric cancer patients. The target gene was searched and identified. The clinicopathologic correlations of the candidate miRNA and target gene were evaluated for their clinical significance. Results: The miR-CGU significantly increases by more than 40.2-fold (p < 0.001) in gastric cancer tissues compared with their matched adjacent nontumorous tissues (n = 109). Overexpression of miRNA was significantly associated with tumor progression that included serosal invasion, lymph node metastasis, distant metastasis and pathological stage (all p < 0.001). Higher expression of miR-CGU was significantly associated with a worse 5-year survival outcome (log rank p < 0.001, and p = 0.005, respectively). Functional assays showed that overexpression of this miRNA enhanced gastric cancer cell migration and invasion in vitro and lung metastasis formation in vivo. In addition, a target gene, ERM protein, was identified for miR-CGU. Elevated expression of miRNA in gastric cancer cells could reduce the mRNA and protein levels of ERM protein, and vice versa. Luciferase assays confirmed that miR-CGU could directly bind to the 2-8 nucleotides of 3’ untranslated region of ERM protein. Moreover, an inverse correlation between miR-CGU and ERM protein expression was observed in gastric cancer tissues. The Interaction of miR-CGU and ERM protein expression was further studied in gastric cell lines. Conclusion: The miR-CGU is highly upreglated in gastric cancer tissues. It functions as a tumor metastasis enhancer in gastric cancer, and its overexpression contributes to lymph node metastasis and progression of gastric cancer. Overexpression of its target gene, ERM protein may have a therapeutic potential to suppress gastric cancer metastasis. Citation Format: Chia-Siu Wang, Ming Ming Tsai, Liang-Mou Kuo, Kwang-Huei Lin. MicroRNA-CGU promotes progression and metastasis through a negative regulation of ERM protein in human 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 5338. doi:10.1158/1538-7445.AM2013-5338