title: MicroRNA genes are frequently located near mouse cancer susceptibility loci.
abstract: MicroRNAs (miRNAs) are short 19- to 24-nt RNA molecules that have been shown to regulate the expression of other genes in a variety of eukaryotic systems. Abnormal expression of miRNAs has been observed in several human cancers, and furthermore, germ-line and somatic mutations in human miRNAs were recently identified in patients with chronic lymphocytic leukemia. Thus, human miRNAs can act as tumor suppressor genes or oncogenes, where mutations, deletions, or amplifications can underlie the development of certain types of leukemia. In addition, previous studies have shown that miRNA expression profiles can distinguish among human solid tumors from different organs. Because a single miRNA can simultaneously influence the expression of two or more protein-coding genes, we hypothesized that miRNAs could be candidate genes for cancer risk. Research in complex trait genetics has demonstrated that genetic background determines cancer susceptibility or resistance in various tissues, such as colon and lung, of different inbred mouse strains. We compared the genome positions of mouse tumor susceptibility loci with those of mouse miRNAs. Here, we report a statistically significant association between the chromosomal location of miRNAs and those of mouse cancer susceptibility loci that influence the development of solid tumors. Furthermore, we identified distinct patterns of flanking DNA sequences for several miRNAs located at or near susceptibility loci in inbred strains with different tumor susceptibilities. These data provide a catalog of miRNA genes in inbred strains that could represent genes involved in the development and penetrance of solid tumors.
authors.affiliation: Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19107, USA.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Sevignani
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Nnadi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shimizu
authors.forename: Ramana V
authors.initials: RV
authors.lastname: Davuluri
authors.forename: Terry
authors.initials: T
authors.lastname: Hyslop
authors.forename: Peter
authors.initials: P
authors.lastname: Demant
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: Linda D
authors.initials: LD
authors.lastname: Siracusa
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002874:Chromosome Mapping; D019992:Databases as Topic; D020022:Genetic Predisposition to Disease; D051379:Mice; D008815:Mice, Inbred Strains; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: D035683:MicroRNAs