title: The rs2910164 G>C polymorphism in microRNA-146a is associated with the incidence of malignant melanoma.
abstract: MicroRNA-146a (miR-146a) is one of the microRNAs (miRNAs) implicated in the pathogenesis of various cancers. Recently, single nucleotide polymorphisms (SNPs) located in miRNAs themselves, so-called MIRSNPs, have attracted attention because of their possible involvement in the pathogenesis of various diseases. Such MIRSNPs may play functional roles because of the alteration of the miRNA. In this study, we investigated whether MIRSNP rs2910164 in miR-146a is involved in the pathogenesis of malignant melanoma (MM). DNA samples were collected from 50 patients with MM and 107 controls and genotyped by a PCR-restriction fragment. In patients with MM, the genotype distributions were 15 CC (30.0%), 35 CG (70.0%), and 0 GG (0.0%). The CG genotype was significantly increased in the patients compared with the controls (P=0.02). The minimum free energy between miR-146a and its complementary strand with the G allele was determined to be -26.8 kcal/mol, whereas that of the C allele was -24.0 kcal/mol, indicating that the change from C to G may increase the stability of the miR-146a. However, there was no significant difference between the CC and the CG genotypes in terms of the relative expression levels of miR-146a. Human melanoma cell lines with the G allele showed significantly higher proliferation, migration, and invasion than those with the C allele. In conclusion, miR-146a may be involved in the pathogenesis of MM, and individuals with the CG genotype have an increased risk of developing MM.
authors.affiliation: Department of Dermatology and Plastic Surgery, Kumamoto University, Kumamoto, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yamashita
authors.forename: Takuma
authors.initials: T
authors.lastname: Iwakiri
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukushima
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Jinnin
authors.forename: Azusa
authors.initials: A
authors.lastname: Miyashita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hamasaki
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Makino
authors.forename: Jun
authors.initials: J
authors.lastname: Aoi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Masuguchi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Inoue
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ihn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012313:RNA / Q000737:chemistry; D012878:Skin Neoplasms / Q000235:genetics*; D018709:Statistics, Nonparametric; D013816:Thermodynamics
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D012313:RNA