Genetic variants in the TGFβ-signaling pathway influence expression of miRNAs in colon and rectal normal mucosa and tumor tissue
| Autor: | Lila E. Mullany, Martha L. Slattery, John R. Stevens, Andromahi Trivellas, Andrew J. Pellatt, Jennifer S. Herrick, Roger K. Wolff |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
TGF-β Male Pathology medicine.medical_specialty Angiogenesis Colorectal cancer Colon colorectal cancer Polymorphism Single Nucleotide Metastasis 03 medical and health sciences 0302 clinical medicine Transforming Growth Factor beta microRNA Carcinoma medicine PTEN Humans Intestinal Mucosa miRNA Aged biology business.industry Rectum Genetic Variation Middle Aged medicine.disease 3. Good health BMPR2 MicroRNAs 030104 developmental biology Oncology 030220 oncology & carcinogenesis eIF4E Cancer research biology.protein Female Signal transduction business Colorectal Neoplasms SMAD Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Martha L. Slattery 1 , Andromahi Trivellas 2 , Andrew J. Pellatt 2 , Lila E. Mullany 1 , John R. Stevens 3 , Roger K. Wolff 1 , Jennifer S. Herrick 1 1 Department of Medicine, University of Utah, Salt Lake City, Utah, USA 2 Tulane Medical School, New Orleans, Louisiana, USA 3 Department of Mathematics and Statistics, Utah State University, Logan, Utah, USA Correspondence to: Martha L. Slattery, email: marty.slattery@hsc.utah.edu Keywords: colorectal cancer, miRNA, TGF-β, eIF4E, SMAD Received: October 13, 2016 Accepted: December 16, 2016 Published: January 05, 2017 ABSTRACT 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. |
| Databáze: | OpenAIRE |
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