PT - JOURNAL ARTICLE AU - Nagel, Remco AU - le Sage, Carlos AU - Diosdado, Begoña AU - van der Waal, Maike AU - Oude Vrielink, Joachim A.F. AU - Bolijn, Anne AU - Meijer, Gerrit A. AU - Agami, Reuven TI - Regulation of the Adenomatous Polyposis Coli Gene by the miR-135 Family in Colorectal Cancer AID - 10.1158/0008-5472.CAN-08-0951 DP - 2008 Jul 15 TA - Cancer Research PG - 5795--5802 VI - 68 IP - 14 4099 - http://cancerres.aacrjournals.org/content/68/14/5795.short 4100 - http://cancerres.aacrjournals.org/content/68/14/5795.full SO - Cancer Res2008 Jul 15; 68 AB - Inactivation of the adenomatous polyposis coli (APC) gene is a major initiating event in colorectal tumorigenesis. Most of the mutations in APC generate premature stop codons leading to truncated proteins that have lost β-catenin binding sites. APC-free β-catenin stimulates the Wnt signaling pathway, leading to active transcription of target genes. In the current study, we describe a novel mechanism for APC regulation. We show that miR-135a&b target the 3′ untranslated region of APC, suppress its expression, and induce downstream Wnt pathway activity. Interestingly, we find a considerable up-regulation of miR-135a&b in colorectal adenomas and carcinomas, which significantly correlated with low APC mRNA levels. This genetic interaction is also preserved in full-blown cancer cell lines expressing miR-135a&b, regardless of the mutational status of APC. Thus, our results uncover a miRNA-mediated mechanism for the control of APC expression and Wnt pathway activity, and suggest its contribution to colorectal cancer pathogenesis. [Cancer Res 2008;68(14):5795–802] ©2008 American Association for Cancer Research.