Trends in Molecular Medicine
ReviewRoles of small RNAs in tumor formation
Section snippets
microRNAs
Over the past decade, in different species and in a range of tissues, several classes of small regulatory RNAs have been identified including miRNAs, small (18–25 nucleotides (nt) in length), noncoding, single-stranded RNAs. MiRNAs negatively regulate gene expression, either by translational inhibition or exonucleolytic mRNA decay, targeted through imperfect complementarity between the miRNA and the 3′ untranslated region (3′UTR) of the mRNA [1]. Depending on the targeted mRNAs, both mechanisms
MiRNA biogenesis: from nucleus to cytoplasm
Since their discovery (Box 1), hundreds of miRNAs have been identified and, at present, the human miRNA database contains 721 miRNAs or approximately 2–3% of the total number of genes in the human genome (Box 2). MiRNAs are produced through a multistep process, including two distinct biogenetic pathways (Figure 1) [extensively reviewed in 4]. During the miRNA maturation processes, transcriptional and post-transcriptional levels are strictly regulated, ensuring precise production. Disruptions in
MiRNA expression in cancer
Although initially identified in B-cell leukemia [5], alterations in the expression of miRNAs are now considered a common characteristic of all human tumors. Compared with normal tissue of the same type, most tumors display a distinct miRNA expression signature (Table 1). In 2006, Lu and collaborators demonstrated that expression profiles of miRNAs could accurately classify human cancers on the basis of their embryonic lineage and differentiation states [6]: tumors of endodermal origin, such as
Causes of abnormal miRNA expression in cancer
Because aberrant miRNA levels are strongly associated with disease, the precise control of miRNA levels is essential for maintaining normal cellular homeostasis. In the following section, we review the major mechanisms involved in miRNA dysregulation in cancer (Figure 2).
Concluding remarks
The rapidly progressing field of small regulatory RNAs continues to reveal the diversity and complexity of the RNA world. However, despite remarkable recent progress, the connection between cancer and miRNAs remains incompletely understood and many important questions remain. First, genome-wide analyses for alterations in miRNA genes or for copy number alterations in various human tumors are needed to identify all of the putative tumor suppressor and oncogenic miRNAs. At the same time, more
Acknowledgements
We sincerely thank Dr Kenneth Nephew for the critical reading of the manuscript and Michela Garofalo and Flavia Pichiorri for suggestions.
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