MicroRNA genes are frequently located near mouse cancer susceptibility loci

Cinzia Sevignani, George A. Calin, Stephanie C. Nnadi, Masayoshi Shimizu, Ramana V. Davuluri, Terry Hyslop, Peter Demant, Carlo M. Croce*, Linda D. Siracusa

*Corresponding author for this work

Research output: Contribution to journalArticle

125 Scopus citations

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, germline 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.

Original languageEnglish (US)
Pages (from-to)8017-8022
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number19
DOIs
StatePublished - May 8 2007

Keywords

  • Inbred strains
  • Quantitative trait loci
  • Solid tumor

ASJC Scopus subject areas

  • General

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    Sevignani, C., Calin, G. A., Nnadi, S. C., Shimizu, M., Davuluri, R. V., Hyslop, T., Demant, P., Croce, C. M., & Siracusa, L. D. (2007). MicroRNA genes are frequently located near mouse cancer susceptibility loci. Proceedings of the National Academy of Sciences of the United States of America, 104(19), 8017-8022. https://doi.org/10.1073/pnas.0702177104