SNP rs1049430 in the 3′-UTR of SH3GL2 regulates its expression: Clinical and prognostic implications in head and neck squamous cell carcinoma
Copyright policy )SNP rs1049430 in the 3′-UTR of SH3GL2 regulates its expression: Clinical and prognostic implications in head and neck squamous cell carcinoma
Single nucleotide polymorphisms (SNPs) in the 3'-UTR region are emerging cis-regulatory factors associated with the occurrences of several human diseases. SH3GL2, which is located at chromosome 9p21-22, is associated with hyperplastic/mildly dysplastic lesions of the head and neck and has a long 3'-UTR with multiple SNPs. The aim of the present study was to determine the susceptible allele(s) in the 3'-UTR SNPs of SH3GL2 in head and neck squamous cell carcinoma (HNSCC). First, we screened the genotypes of all SNPs located in the 3'-UTR of SH3GL2 in 110 controls and 147 cases in Indian populations by sequencing. A SNP (rs1049430:>G/T) that showed only heterozygosity was further confirmed by genotyping with an Illumina GoldenGate platform in 530 controls and 764 cases. Genotype-specific survival analysis of the HNSCC patients was performed. In addition, genotype-specific mRNA stability, isoform expression and protein expression were analyzed. SNP rs1049430 was not associated with disease occurrence, but it was associated with poor patient outcome. The G allele was associated with decreased SH3GL2 mRNA stability, differential splicing and low protein expression. Thus, our data demonstrate that the presence of the susceptible G allele in SNP rs1049430 is associated with the inactivation of SH3GL2 and could be used as a prognostic marker of HNSCC.
- Johns Hopkins University United States
- Indian Institute of Chemical Biology India
- Johns Hopkins Medicine United States
- Council of Scientific and Industrial Research India
- Institute of Genomics and Integrative Biology India
Adult, Male, Genotype, 3′-UTR, Kaplan-Meier Estimate, HNSCC, Polymorphism, Single Nucleotide, Gene Frequency, Cell Line, Tumor, Humans, Genetic Predisposition to Disease, Molecular Biology, 3' Untranslated Regions, Alleles, Adaptor Proteins, Signal Transducing, Aged, Aged, 80 and over, rs1049430, Middle Aged, SH3GL2, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms, Allele-specific isoform, Carcinoma, Squamous Cell, MCF-7 Cells, Molecular Medicine, Female
Adult, Male, Genotype, 3′-UTR, Kaplan-Meier Estimate, HNSCC, Polymorphism, Single Nucleotide, Gene Frequency, Cell Line, Tumor, Humans, Genetic Predisposition to Disease, Molecular Biology, 3' Untranslated Regions, Alleles, Adaptor Proteins, Signal Transducing, Aged, Aged, 80 and over, rs1049430, Middle Aged, SH3GL2, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms, Allele-specific isoform, Carcinoma, Squamous Cell, MCF-7 Cells, Molecular Medicine, Female
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