Document Type

Article

Publication Date

May 2007

Comments

This article has been peer reviewed. It is the authors' final version prior to publication in Proc Natl Acad Sci U S A. 2007 May 8;104(19):8017-22. Epub 2007 Apr 30. The published version is available at www.pnas.org./cgi/content/abstract/104/19/8017

Construction of the MUSMIRSUS Database.

A total of 229 mouse miRNA gene locations were downloaded from the July 2005 miRNA registry web site (microrna.sanger.ac.uk). We combined and compared the Mb positions of mouse miRNAs with those of known susceptibility and modifier loci (www.ensembl.org); this ordered list was used to identify miRNAs that mapped at or near the peak of tumor loci.

The database was named MUSMIRSUS, for Mus miRNA susceptibility and is contained in its entirety at www.kimmelcancercenter.org/siracusa/musmirsus.htm.

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.

Additional Files
sevignani-fig1.gif (40 kB)
Figure 1
sevignani-fig2.gif (9 kB)
Figure 2
sevignani-fig3.gif (148 kB)
Figure 3
sevignani-table1.gif (27 kB)
Table 1
Download

Share

COinS