Colorectal cancer (CRC) is one of the leading causes of cancer death in Western countries. A significant number of CRC patients undergoing curative-intented surgery subsequently develop recurrence and die from the disease. MicroRNAs (miRNAs) are aberrantly expressed in cancers and appear to have both diagnostic and prognostic significance. In this study we identified novel miRNAs associated with recurrence of CRC. TaqMan® Human MicroRNA Array Set v2.0 was used to profile the expression of 667 miRNAs in 14 normal colon mucosas and 46 microsatellite stable CRC tumors. Four miRNAs (miR-362-3p, miR-570, miR-148a* and miR-944) were expressed at a lower level in the tumors from patients with recurrence (p < 0.015) compared to tumors from patients with no recurrence. A significant association of low expression with reduced disease free survival was confirmed for miR-362-3p in a second independent cohort of 43 CRC patients using single TaqMan® microRNA assays. In vitro functional analysis showed that over-expression of miR-362-3p in colon cancer cell lines (HCT116, LS174T, and DLD1) reduced cell viability and proliferation mainly due to cell cycle arrest. E2F1, USF2 and PTPN1 were identified as potential miR-362-3p targets by mRNA profiling of HCT116 cells over-expressing miR-362-3p. Subsequently, these genes were confirmed as direct targets by Luciferase reporter assays. In vitro knock-down confirmed that these targets are important players in the miR-362-3p target network. We conclude that miR-362-3p may be a novel prognostic marker in CRC and hypothesize that augmented expression of miR-362-3p may prevent the development of distant metastasis by targeting E2F1, USF2 and PTPN1.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4138. doi:1538-7445.AM2012-4138