Cancer-associated genomic regions (CAGRs) and noncoding RNAs: bioinformatics and therapeutic implications Simona Rossi Cinzia Sevignani Stephanie C. Nnadi Linda D. Siracusa George A. Calin Received: 18 April 2008 / Accepted: 22 May 2008 Ó Springer Science+Business Media, LLC 2008 Abstract MicroRNAs (miRNAs) are small noncoding RNAs (ncRNAs, RNAs that do not code for proteins) that regulate the expression of target genes at the posttran- scriptional 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 abnor- malities 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. Noncoding RNAs and bioinformatics Recent biotechnology advances, along with a growing number of new biological-computational approaches, have allowed an expansion of the number of genomes being sequenced and annotated, as well as facilitated the devel- opment of databases to collect and analyze large amounts of genetic information. The consequent necessities of retrieving, sharing, and, in particular, understanding this vast amount of data led to the creation of genome dat- abases, providing an open source of genetic information for scientists worldwide. Thus, there is now a strong urgency to integrate various sources of biomedical and clinical information. One of the many fields that will strongly benefit from such integration is the study of noncoding RNAs (ncR- NAs) (Barbarotto et al. 2008; Calin and Croce 2006a; Esquela-Kerscher and Slack 2006). The most studied ncRNAs are the microRNAs (miRNAs),19–24-nucleotide (nt) transcripts that regulate the expression of target S. Rossi  G. A. Calin (&) Department of Experimental Therapeutics, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA e-mail: gcalin@mdanderson.org S. Rossi Department of Morphology and Embryology, University of Ferrara, Ferrara 44100, Italy C. Sevignani  S. C. Nnadi  L. D. Siracusa (&) Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, BLSB 719, Philadelphia, PA 19107-5541, USA e-mail: Siracusa@mail.jci.tju.edu G. A. Calin Department of Cancer Genetics, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA 123 Mamm Genome DOI 10.1007/s00335-008-9119-8