Slattery Martha L, Trivellas Andromahi, Pellatt Andrew J, Mullany Lila E, Stevens John R, Wolff Roger K, Herrick Jennifer S
Department of Medicine, University of Utah, Salt Lake City, Utah, USA.
Tulane Medical School, New Orleans, Louisiana, USA.
Oncotarget. 2017 Mar 7;8(10):16765-16783. doi: 10.18632/oncotarget.14508.
The TGF-β signaling pathway is involved in regulation of cell growth, angiogenesis, and metastasis. We test the hypothesis that genetic variation in the TGF-β signaling pathway alters miRNA expression.We use data from 1188 colorectal cancer cases to evaluate associations between 80 SNPs in 21 genes.Seven variants eIF4E rs12498533, NFκB1 rs230510, TGFB1 rs4803455, TGFBR1 rs1571590 and rs6478974, SMAD3 rs3743343, and RUNX1 rs8134179 were associated with expression level of miRNAs in normal colorectal mucosa. RUNX2 rs12333172 and BMPR1B rs13134042 were associated with miRNAs in normal colon mucosa; eIF4EBP3 rs250425, SMAD3 rs12904944, SMAD7 rs3736242, and PTEN rs532678 were associated with miRNA expression in normal rectal mucosa. Evaluation of the differential expression between carcinoma and normal mucosa showed that SMAD3 rs12708491 and rs2414937, NFκB1 rs230510 and rs3821958, and RUNX3 rs6672420 were associated with several miRNAs for colorectal carcinoma. Evaluation of site-specific differential miRNA expression showed that BMPR1B rs2120834, BMPR2 rs2228545, and eIF4EBP3 rs250425 were associated with differential miRNA expression in colon tissue and SMAD3 rs12901071, rs1498506, and rs2414937, BMPR2 rs2228545, and RUNX2 rs2819854, altered differential miRNA expression in rectal tissue.These data support the importance of the TGF-β signaling pathway to the carcinogenic process, possibly through their influence on miRNA expression levels.
转化生长因子-β（TGF-β）信号通路参与细胞生长、血管生成和转移的调控。我们检验了TGF-β信号通路中的基因变异会改变微小RNA（miRNA）表达这一假说。我们使用来自1188例结直肠癌病例的数据来评估21个基因中80个单核苷酸多态性（SNP）之间的关联。七个变异体，即真核翻译起始因子4E（eIF4E）rs12498533、核因子κB1（NFκB1）rs230510、转化生长因子β1（TGFB1）rs4803455、转化生长因子β受体1（TGFBR1）rs1571590和rs6478974、SMAD家族成员3（SMAD3）rs3743343以及RUNX1 rs8134179与正常结直肠黏膜中miRNA的表达水平相关。RUNX2 rs12333172和骨形态发生蛋白受体1B（BMPR1B）rs13134042与正常结肠黏膜中的miRNA相关；eIF4E结合蛋白3（eIF4EBP3）rs250425、SMAD3 rs12904944、SMAD7 rs3736242和磷酸酶及张力蛋白同源物（PTEN）rs532678与正常直肠黏膜中的miRNA表达相关。癌组织与正常黏膜之间差异表达的评估表明，SMAD3 rs12708491和rs2414937、NFκB1 rs230510和rs3821958以及RUNX3 rs6672420与结直肠癌的几种miRNA相关。位点特异性差异miRNA表达的评估表明，BMPR1B rs2120834、骨形态发生蛋白受体2（BMPR2）rs2228545和eIF4EBP3 rs250425与结肠组织中差异miRNA表达相关，而SMAD3 rs12901071、rs1498506和rs2414937、BMPR2 rs2228545以及RUNX2 rs2819854改变了直肠组织中差异miRNA表达。这些数据支持TGF-β信号通路对致癌过程的重要性，可能是通过其对miRNA表达水平的影响。
