Circulating MicroRNA in Digestive Tract Cancers

Abstract

d t For many decades, cell-free nucleic acids have been known to be present in peripheral blood. Several tudies have identified tumor-specific and/or tumor-assoiated alterations in the circulating nucleic acids of paients with various cancers. In recent years, cell-free miroRNA (miRNA) have been stably detected in the plasma nd serum, like other molecules; their presence in the lood has attracted the attention of researchers due to heir potential use as valuable blood biomarkers.1 MiRNAs are short, noncoding RNAs that play important roles in various physiologic and developmental processes. The mature miRNAs are produced from long primary transcripts through 2 sequential cleavage steps. The long primary miRNA transcript is cleaved by the Drosha complex in the nucleus, generating intermediate precursor miRNA. Precursor miRNA is transported by exportin-5 from the nucleus into the cytoplasm, and then subjected to further cleavage by a Dicer RNAase III enzyme, generating a short double-strand miRNA. One strand (guided strand) of mature miRNA is then incorporated into the RNA-induced silencing complex and subsequently hybridize to the 3=-untranslated region of their target mRNAs to repress translation or degrade these mRNAs. Thus, a single miRNA can influence the expression of hundreds of genes and allow them to function in a coordinated manner. Therefore, miRNAs have been implicated as key molecules in all cellular processes. Numerous studies have shown that alterations in miRNA expression correlate with various diseases, including the development and progression of cancer, and some miRNAs can function as oncogenes or tumor suppressors. These findings have opened up a new and interesting field in the diagnosis of cancer and the treatments of cancer patients. Mitchell et al2 first demonstrated that circulating miRNAs had the potential to be new biomarkers in patients with solid cancers. In recent years, several papers have demonstrated that circulating miRNAs can also be detected in the peripheral blood of patients with digestive tract cancers. Although the origins and physiologic functions of cell-free miRNAs in the blood remain to be fully elucidated, a noninvasive assay for miRNAs should be developed to exploit these molecules as potential diagnostic and prognostic biomarkers. This assay undoubtedly contributes to an improvement in the clinical outcomes of cancer patients. In this article, we review the current state of biological and clinical research regarding circulating miRNAs of digestive tract cancer patients and discuss the future perspectives.