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