One wrong snip from your barber might leave you with a bad hair day, but a genomic SNP in the wrong place, like a miRNA target site, can leave you in a much worse situation; with a predisposition to cancer.
SNPs have been studied extensively in several diseases, but only recently have scientists started looking at how SNPs effect miRNA regulation. Because of the short length of miRNAs, one SNP within a miRNA target binding site can have a big impact; creating, removing or altering the site. In a new publication, a team of researchers working out of the University of Texas- M.D. Anderson Cancer Center and The Wister Institute (and several other places) set out to confirm the link between SNPs, miRNA regulation and breast cancer.
The group analyzed SNPs associated with breast cancer susceptibility looking for changes in miRNA binding sites, and miRNA::mRNA gene regulation. Here is some of what they found out:
- TGFB1 SNP rs1982073 effected miR-187, and rs1799782 within XRCC1 effected miR-138 interactions.
- About 15% (2/14) of transcribed SNPs tested were shown to be associated with breast cancer through interference of miRNA binding. This low number is possibly due to poor accuracy of miRNA target predictions.
- A group of SNPs, ID’d through bioinformatics, as putative modifiers of miRNA binding sites, and sorted them by genomic location (3’ UTR, 5’ UTR or CDS).
- Target SNPs have differential distribution within breast cancer and control populations.
- Target SNPs in BRCA1, TGFBR1 and XIAP were validated by in vitro luciferase reporter assays, and then they further showed that those SNPs led to a reduction of the endogenous protein levels, confirming the SNP::miRNA::mRNA connection.
This area is bound to heat up as more miRNAs, SNPs and target sites are found daily. Stay up-to-date, and see all of the details in Cancer Research, April 2010.