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Cancer-associated genomic regions (CAGRs) and noncoding RNAs: bioinformatics and therapeutic implications

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Abstract

MicroRNAs (miRNAs) are small noncoding RNAs (ncRNAs, RNAs that do not code for proteins) that regulate the expression of target genes at the posttranscriptional or posttranslational level. Many miRNAs have conserved sequences between distantly related organisms, suggesting that these molecules participate in essential developmental and physiologic processes. miRNAs can act as tumor suppressor genes or oncogenes in human cancers. Mutations, deletions, or amplifications have been found in human cancers and shown to alter expression levels of mature and/or precursor miRNA transcripts. Moreover, a large fraction of genomic ultraconserved regions (UCRs) encode a particular set of ncRNAs whose expression is altered in human cancers. Both miRNAs and UCRs are frequently located at fragile sites and genomic regions affected in various cancers, named cancer-associated genomic regions (CAGRs). Bioinformatics studies are emerging as important tools to identify associations and/or correlations between miRNAs/ncRNAs and CAGRs. ncRNA profiling has allowed the identification of specific signatures associated with diagnosis, prognosis, and response to treatment of human tumors. Several abnormalities could contribute to the alteration of miRNA expression profiles in each kind of tumor and in each kind of tissue. This review is focused on the miRNAs and ncRNAs as genes affecting cancer risk, and we provided an updated catalog of miRNAs and UCRs located at fragile sites or at cancer susceptibility loci. These types of studies are the first step toward discoveries leading to novel approaches for cancer therapies.

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Acknowledgments

Dr. Calin was supported by the CLL Global Research Foundation, in part by the Fellow of The University of Texas M.D. Anderson Research Trust, and by the Ladjevardian Regent Research Scholar Fund. Dr. Siracusa was supported by NCI grants RO1 CA86560 and CA120243.

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Authors and Affiliations

  1. Department of Experimental Therapeutics, MD Anderson Cancer Center, University of Texas, Houston, TX, 77030, USA

    Simona Rossi & George A. Calin

  2. Department of Morphology and Embryology, University of Ferrara, Ferrara, 44100, Italy

    Simona Rossi

  3. Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, BLSB 719, Philadelphia, PA, 19107-5541, USA

    Cinzia Sevignani, Stephanie C. Nnadi & Linda D. Siracusa

  4. Department of Cancer Genetics, MD Anderson Cancer Center, University of Texas, Houston, TX, 77030, USA

    George A. Calin

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  1. Simona Rossi
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  2. Cinzia Sevignani
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  3. Stephanie C. Nnadi
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  4. Linda D. Siracusa
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  5. George A. Calin
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Correspondence to Linda D. Siracusa or George A. Calin.

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Rossi, S., Sevignani, C., Nnadi, S.C. et al. Cancer-associated genomic regions (CAGRs) and noncoding RNAs: bioinformatics and therapeutic implications. Mamm Genome 19, 526–540 (2008). https://doi.org/10.1007/s00335-008-9119-8

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  • DOI: https://doi.org/10.1007/s00335-008-9119-8

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