Abstract. Drosha and Dicer are important regulators of microRNA (miRNA) biogenesis, and it has been suggested that their aberrant regulation may cause colorectal cancer (CRC). The aim of the present study was to evaluate the mRNA expression levels of these two important RNase III nucleases and their association with clinical features in CRC specimens from South Korean patients. The expression levels of Drosha and Dicer mRNA were investigated in 77 CRC tissues and adjacent histologically non-neoplastic tissues using the quantitative polymerase chain reaction. The expression levels of Drosha and Dicer mRNA were identified to be upregulated in CRC. Neither the Drosha nor the Dicer mRNA expression level was associated with any clinical parameter, including sex, age, TNM stage, body mass index and carcinoembryonic antigen titer in patients with CRC. Furthermore, the expression levels of Drosha and Dicer mRNA were not associated with each other. The miRNA biogenesis-associated RNase III nucleases Drosha and Dicer are significantly upregulated in CRC, suggesting their importance in the pathobiology of colorectal carcinogenesis.
IntroductionColorectal carcinoma (CRC) is the third most common cancer in Western countries and South Korea (1,2). CRC is also one of the primary causes of cancer mortality worldwide (1,3). The pathogenesis of CRC has been reported to be complicated and tightly controlled by various mechanisms, including genome structural rearrangements, chromatin remodeling, genetic mutations and epigenetic alterations (4,5).MicroRNAs (miRNAs), which are small RNA molecules that serve an essential role in fine-tuning gene expression, regulate a range of biological processes, including cellular development, differentiation, proliferation, K + channel modulation, stress responses, DNA repair, cell adhesion, cell death, inflammation, metabolism and tumor development (6-9). It has been identified that appropriate and physiological miRNA biogenesis is controlled by an elaborate and well-regulated process, referred to as the 'miRNA machinery' pathway (10). This signaling pathway is regulated by various components, including Drosha, DiGeorge syndrome critical region gene 8 (DGCR8), exportin-5 (Xpo5), Dicer, transactivation-responsive RNA-binding protein (TRBP) and Argonaute (AGO). Among these, Drosha and Dicer are important regulators of miRNA biogenesis. In the nucleus, primary miRNAs (RNA extensions several hundred nucleotides long) are processed into precursor miRNAs (pre-miRNAs; stem-loop structures of between 70 and 100 nucleotides) by RNase III Drosha (11). These pre-miRNAs are then processed by another RNase III, Dicer, into mature miRNAs within the cytoplasm (12).As disruption of the miRNA machinery pathway has been suggested to be involved in cancer (13), a number of studies have demonstrated the expression and the clinical implications of the components of the miRNA machinery pathway in CRC. For instance, Faber et al (14) identified that overexpressed Dicer is significantly associated with poor survival and...