Expressional profiling of prostate cancer risk SNPs at 11q13.5 identifies DGAT2 as a new target gene

Abstract

A total of nine non-coding variants on 11q13.5 predispose men to prostate cancer (PrCa). rs200331695 within the EMSY intron is associated with aggressive PrCa and two high linkage disequilibrium (LD) groups of single-nucleotide polymorphisms (SNPs) in the intergenic region are associated with PrCa death. Here, the cis-effect of the SNPs on gene expression using expression quantitative trait loci analysis was investigated. The regulatory potential was screened in prostate tumors (n = 41) and in whole blood (n = 99). The results were validated in a second tumor set (n = 41), in lymphoblastoid cell lines (LCLs) (n = 38), and using the GTEx Portal. The effects of haplotypes were analyzed in the whole blood. The high LD SNPs (rs143975731, rs12277366, rs2155225, and rs2155222) were associated with DGAT2 expression in both tumors sets (screening P = 0.035-0.043; validation P = 0.005-0.018). The PrCa death-associated alleles decreased the expression by two-fold. rs200331695 decreased DGAT2 expression in LCLs (P = 0.006). The findings of SNPs regulating CAPN5 (P = 0.026-0.046) and AP001189.4 (P = 0.03-0.039) in the whole blood were not observed in LCLs, but the association with AP001189.4 expression was validated via the GTEx Portal (P = 8.7 × 10(-5) to 4.3 × 10(-4) ), which suggests that the high LD intergenic SNPs exert a tissue-dependent effect on the expression of two genes. No haplotypes including the risk SNPs at 11q13.5 were associated with gene expression and PrCa. The findings indicate the functionality of the PrCa death-predisposing SNPs rs143975731, rs12277366, rs2155225, and rs2155222 as DGAT2 regulators in prostate tumors. © 2016 Wiley Periodicals, Inc.

DGUOK‐AS1 promotes cell proliferation in cervical cancer via acting as a ceRNA of miR‐653‐5p

“…EMSY is a putative target gene of miR‐653‐5p, and its oncogene role in cancers has been reported . In the current study, we demonstrated that EMSY was negatively regulated by miR‐653‐5p and EMSY silence led to attenuation of CC cell growth.…”

Comprehensive Genetic Analysis of DGAT2 Mutations and Gene Expression Patterns in Human Cancers

“…This does not appear to be cancer specific. We found this paradoxical since several studies have shown that DGAT2 overexpression inhibits cell proliferation [ 10 , 31 , 35 ].…”

“…NCBI does not list clinical significance for any of the eight SNPs nor could we find any literature describing the phenotypes of these alleles. However, one publication does report several intergenic SNPs associated with decreased DGAT2 expression, which promotes predisposition to prostate cancer [ 35 ]. We investigated expression data for DGAT2 mutations (see Section 3.7 ) and indeed, one of the alleles (R218W, rs528376420) appears to show increased expression levels, though the results are highly variable and not statistically significant under our analysis.…”