Many studies have highlighted the role that microRNAs have in physiological processes and how their deregulation can lead to cancer. More recently it has been proposed that the presence of single nucleotide polymorphisms in microRNA genes, their processing machinery and target binding sites affects cancer risk, treatment efficacy and patient prognosis. In reviewing this new field of cancer biology, we describe the methodological approaches of these studies and make recommendations for which strategies will be most informative in the future.Human populations are estimated to be 99% identical at the level of the genetic code; thus, human diversity (other than epigenetics) arises from the remaining 1% of variation 1 , most of which is due to single nucleotide polymorphisms (SNPs). These are a non-repetitive form of sequence variation that was first identified in 1978 in the β-globin gene cluster2. To date, approximately 10 million SNPs have been identified in the human genome, occurring on average every 100 to 300 base pairs (International HapMap Project website; see Further information) 1,3 . Although most SNPs are silent, epidemiological studies have established a link between variations in gene sequence, environmental interaction and cancer risk. By identifying genetic markers of susceptibility and characterizing gene-environment © 2010 Macmillan Publishers Limited. All rights reserved Correspondence to C.C.H. Curtis_Harris@nih.gov . Competing interests statementThe authors declare no competing financial interests. DATABASES NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript interactions, it might be possible to reduce cancer mortality through early diagnosis and personalized therapy.As our knowledge of the topology of the genome has evolved, a new class of non-coding RNAs has emerged called microRNAs (miRNAs). The latest release of the miRBase database has catalogued 721 human miRNAs. Smaller than protein-coding genes, miRNAs can regulate the translation of hundreds of genes through sequence-specific binding to mRNA4, and depending on the degree of sequence complimentary will result in the inhibition of translation and/or degradation of target mRNAs4 , 5. Interestingly, a recent report shows that miR-369-3p can upregulate the expression of its target, tumour necrosis factor-α (TNFα)6.Our knowledge and understanding of miRNA biogenesis has evolved in recent years, and is thoroughly described elsewhere 4,7 (FIG. 1). Briefly, mature miRNAs are short RNA molecules of between 19 and 22 nucleotides in length. Nucleotides 2-7 of the mature miRNA sequence create the 'seed region' ) that primarily specifies the specific mRNA that the miRNA will bind. The degree of specificity conferred by the seed region is comparable to that of the DNA sites recognized by transcription factors12. Although the binding between the seed region is (mostly) in perfect Watson-Crick complementarity, flanking regions do not have to bind with equal precision. In an additional analogy to transcription factors, it ...
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