Exon skipping of midkine pre-mRNA is enhanced by intronic polymorphism in a colon cancer cell line

A correlation between the polymorphism, heterogeneous G/T at the 62nd site of intron 3 in the midkine gene, and the induction of colorectal cancer has been reported [Cancer Lett. 180 (2002) 159]. The minigene containing exons 2, 3 and 4, as well as intronic sequences flanking exon 3, was transfected into COLO205 colon cancer cells. When the base of the site was G, correctly spliced mRNA was strongly detected. However in case of a G to T substitution, a truncated exon 3 mRNA was strongly detected. In this case, the detection of correctly spliced mRNA was weak. When the minigene was transfected into HCT-15 colon cancer cells, correctly spliced mRNA was strongly detected in the cases of both minigenes. This indicates the possibility that a G to T substitution at the 62nd site of intron 3 in the midkine gene enhances the expression of truncated midkine in colon cancer.