title: 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.
abstract: 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.
authors.affiliation: Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital and Institute, Tianjin 300060, People's Republic of China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.forename: Yuexin
authors.initials: Y
authors.lastname: Liu
authors.forename: Fengju
authors.initials: F
authors.lastname: Song
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Limei
authors.initials: L
authors.lastname: Hu
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.forename: Peifang
authors.initials: P
authors.lastname: Liu
authors.forename: Xishan
authors.initials: X
authors.lastname: Hao
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Kexin
authors.initials: K
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D044466:Asian People; D001665:Binding Sites / Q000235:genetics; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002114:Calcinosis / Q000209:etiology* / Q000235:genetics; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D005838:Genotype; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger; D012306:Risk; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D015996:Survival Rate
chemical_list: D020413:3' Untranslated Regions; C568081:MIRN367 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel