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SNPs in microRNA and microRNA Target Sites Associated with Human Cancers

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Current Perspectives in microRNAs (miRNA)

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MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in gene regulatory network. They regulate gene expression at the post-transcriptional level by base-pairing to the 3′-untraslated region (3′-UTR) of their target messenger RNAs (mRNAs), thus leading to mRNA degradation or repressed protein production. The expression of miRNA is deregulated in many types of cancers. However, whether miRNA mutations and single nucleotide polymorphisms (SNPs) are associated with cancers remains obscure. We have systematically screened mutations and SNPs of both miRNAs and their targets in human cancers by mining public databases and genotyping. We identified several mutations/SNPs of miRNA genes in human colon and prostate cancer tissues and cell lines. These mutations/SNPs are located either at regions of mature miRNAs, or of miRNA precursors (pre-miRNAs) or of primary transcripts (pri-miRNAs). MiRNA mutations/SNPs might disrupt miRNA functions by affecting miRNA transcription, miRNA bio-processing or miRNA-target interaction. We found that the density of SNPs at miRNA-binding sites of miRNA targets is significantly lower than that of SNPs located in the 3′-UTRs of human genes, suggesting that miRNA target SNPs underwent a purifying selection during evolution. This result further indicates important biological functions and therefore potential pathological functions of human miRNAs. Indeed, we found that the allele frequencies of several miRNA target SNPs is aberrant in human cancers. Some SNPs might affect miRNA-target interaction and thus target expression. The contribution of these mutations/SNPs of miRNAs and miRNA targets to carcinogenesis is currently under investigation.

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Authors and Affiliations

  1. Health Sector, Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montréal, Québec, H4P 2R2, Canada

    Shi-Hsiang Shen & Zhenbao Yu

  2. Department of Medicine, McGill University, Montréal, Québec, H3G 1A4, Canada

    Shi-Hsiang Shen

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  1. Shi-Hsiang Shen
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  1. University of Southern California, Los Angeles, CA, USA

    Shao-Yao Ying

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Shen, SH., Yu, Z. (2008). SNPs in microRNA and microRNA Target Sites Associated with Human Cancers. In: Ying, SY. (eds) Current Perspectives in microRNAs (miRNA). Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-8533-8_16

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