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Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13653-8. doi: 10.1073/pnas.1103360108. Epub 2011 Aug 2.

Functional SNP in the microRNA-367 binding site in the 3'UTR of the calcium channel ryanodine receptor gene 3 (RYR3) affects breast cancer risk and calcification.

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Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital and Institute, Tianjin 300060, People's Republic of China.


We have evaluated and provided evidence that the ryanodine receptor 3 gene (RYR3), which encodes a large protein that forms a calcium channel, is important for the growth, morphology, and migration of breast cancer cells. A putative binding site for microRNA-367 (miR-367) exists in the 3'UTR of RYR3, and a genetic variant, rs1044129 A→G, is present in this binding region. We confirmed that miR-367 regulates the expression of a reporter gene driven by the RYR3 3'UTR and that the regulation was affected by the RYR3 genotype. A thermodynamic model based on base pairing and the secondary structure of the RYR3 mRNA and miR-367 miRNA showed that miR-367 had a higher binding affinity for the A genotype than for the G genotype. The rs1044129 SNP was genotyped in 1,532 breast cancer cases and 1,600 healthy Chinese women. The results showed that compared with the AA genotype, G was a risk genotype for breast cancer development and was also associated with breast cancer calcification and poor survival. Thus, rs1044129 is a unique SNP that resides in a miRNA-gene regulatory loop that affects breast cancer risk, calcification, and survival.

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