Abstract 1483: Biological and clinical significance of miR-224 in colorectal cancer

Abstract MicroRNAs (miRNAs) not only participate to cancer initiation and tumor growth, but also play roles in tumor metastasis. The aims of this study were to identify specific miRNAs involved in colorectal cancer (CRC) metastasis, and study their biological functions. We initially assessed by microarray global miRNA expression profile in primary CRC tissues from patients with or without metastasis. The most differentially expressed miRNAs were validated in a large set of CRC patient samples by real time PCR (qRT-PCR). We identified 7 miRNAs that were significantly upregulated in stage III-IV primary CRC compared with stage I-II cancer, among which miR-224 expression increased consistently with tumor burden. We used transwell-based cell motility analysis in CRC cell lines to test the biological activities of studied miRNAs, and showed that miR-224 and miR-141 promote CRC cell motility. By using qRT-PCR, western blot and luciferase assay, we identified SMAD4 as a direct miR-224 target mediating miR-224's effect on cell motility in CRC cells. We conclude that MiR-224 is associated with CRC malignancy, and functions as a metastasis activator by negative regulation of SMAD4. Citation Format: HUI LING, George Calin, Milena Nicoloso, Mariko Ikuo. Biological and clinical significance of miR-224 in colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1483. doi:10.1158/1538-7445.AM2014-1483