Abstract 2300: MicroRNA-101 (miR-101) posttranscriptionally regulates the expression of EP4 receptor in colon cancers

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL The predominant product of cyclooxygenase (COX-2) in the colon, prostaglandin (PG) E2 promotes carcinogenesis. Expression of the PGE2 receptor EP4 is upregulated during colorectal carcinogenesis. However the mechanism leading to deregulation of the EP4 receptor is not known. The present study was conducted to investigate the regulation of EP4 receptor by miRNAs. A bioinformatics search revealed a conserved target site for miR-101 within the EP4 receptor-3′ UTR. In both colorectal cancer cell lines and human specimens, we observed an inverse correlation between miR-101 and EP4 receptor protein. Transfection of LS174T cells with miR-101 significantly suppressed a luciferase reporter containing the EP4 receptor-3′-UTR. In contrast, a mutant EP4 receptor-3′-UTR was unaffected. Ectopic expression miR-101 markedly reduced cell proliferation and motility. Co-transfection of EP4 receptor could rescue colon cancer cells from the tumor suppressive effects of miR-101. Moreover, pharmacologic inhibition of EP4 receptor signaling or silencing of EP4 receptor phenocopied the effect of miR-101. This is the first study to show that the EP4 receptor is negatively regulated by miR-101. 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 2300. doi:1538-7445.AM2012-2300