A Distinct Expression Pattern of the Long 3′-Untranslated Region Dicer mRNA and Its Implications for Posttranscriptional Regulation in Colorectal Cancer

Abstract

OBJECTIVES:Reduced expression of Dicer is associated with global downregulation of microRNAs. Primary Dicer transcripts can be processed at two alternative polyadenylation sites, generating two pools of messenger RNAs (mRNAs) that carry either a long or a short 3′-untranslated regions (3′UTRs), that both encode the same Dicer protein. The short 3′UTR Dicer mRNA is not regulated by miR-103/107. The aim of this study was to investigate the expression of total Dicer mRNA, long 3′UTR Dicer mRNA, and miR-103 in colorectal cancer (CRC).METHODS:Paired tumor and normal mucosal specimens were obtained from 66 patients with CRC. Real-time reverse transcription PCR of long 3′UTR Dicer mRNA, total Dicer mRNA and miR-103 was carried out using the TaqMan Expression assay and the TaqMan MicroRNA assay.RESULTS:The median expression level of coding Dicer mRNA in the tumors was significantly lower than that in normal mucosa (P<0.001). There was no significant difference in expression levels of long 3′UTR Dicer mRNA between the tumors and the normal mucosa (P=0.90). The median expression ratio of long 3′UTR Dicer mRNA to total Dicer mRNA in tumors was significantly higher than in normal mucosa (P<0.001). There was no significant difference in expression levels of miR-103 between the tumors and normal mucosa (P=0.17). There was no significant correlation between clinicopathological findings, such as stage, tumor location, and histological grade and expression levels of total Dicer mRNA, long 3′UTR Dicer mRNA, or expression ratio of long 3′UTR Dicer mRNA to total Dicer mRNA.CONCLUSIONS:These results suggest that both transcriptional and posttranscriptional dysregulation of Dicer expression may be involved in colon carcinogenesis.