SND1, a Component of RNA-Induced Silencing Complex, Is Up-regulated in Human Colon Cancers and Implicated in Early Stage Colon Carcinogenesis

摘要: Colon cancers have been shown to develop after accumulation of multiple genetic and epigenetic alterations with changes in global gene expression profiles, contributing the establishment widely diverse phenotypes. Transcriptional posttranscriptional regulation by small RNA species, such as interfering microRNA RNA-induced silencing complex (RISC), is currently drawing major interest regard cancer development. SND1, also called Tudor-SN p100 recently reported be a component RISC, among list highly expressed genes human colon cancers. In present study, we showed remarkable up-regulation SND1 mRNA tissues, even early-stage lesions, cell lines. When mouse Snd1 was stably overexpressed IEC6 rat intestinal epithelial cells, contact inhibition lost growth promoted, cells became confluent. Intriguingly, high levels an altered distribution E-cadherin from membrane cytoplasm, suggesting loss cellular polarity. Furthermore, adenomatous polyposis coli (Apc) protein coincidentally down-regulated, no significant Apc level. Immunohistochemical analysis using chemically induced colonic lesions developed rats revealed overexpression not only but aberrant crypt foci, putative precancerous colon. Up-regulation may thus occur at very early stage carcinogenesis contribute key players development, including APC β-catenin. [Cancer Res 2007;67(19):9568–76]