MNS16A tandem repeat minisatellite of human telomerase gene: functional studies in colorectal, lung and prostate cancer
| Autor: | Cornelia Zöchmeister, Stefanie Brezina, Andreas Baierl, Hedwig Sutterlüty-Fall, Angelina Doriguzzi, Christian Behm, Vanita Vanas, Philipp Hofer, Andrea Gsur, Klaus Holzmann |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Telomerase Lung Neoplasms Minisatellite Repeat Minisatellite Repeats Biology functional polymorphism telomerase 03 medical and health sciences 0302 clinical medicine Tandem repeat Cell Line Tumor medicine Humans Telomerase reverse transcriptase Promoter Regions Genetic MNS16A TERT regulation Binding Sites Polymorphism Genetic Genetic Variation Prostatic Neoplasms Cancer Promoter medicine.disease Molecular biology Gene Expression Regulation Neoplastic DNA binding site Variable number tandem repeat 030104 developmental biology Oncology 030220 oncology & carcinogenesis Female Colorectal Neoplasms Research Paper Protein Binding Transcription Factors |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Philipp Hofer 1 , Cornelia Zochmeister 1 , Christian Behm 1 , Stefanie Brezina 1 , Andreas Baierl 2 , Angelina Doriguzzi 1 , Vanita Vanas 1 , Klaus Holzmann 1 , Hedwig Sutterluty-Fall 1 , Andrea Gsur 1 1 Medical University of Vienna, Institute of Cancer Research, A-1090 Vienna, Austria 2 University of Vienna, Department of Statistics and Operations Research, A-1010 Vienna, Austria Correspondence to: Andrea Gsur, email: andrea.gsur@meduniwien.ac.at Keywords: genetic variation, MNS16A, functional polymorphism, telomerase, TERT regulation Received: September 23, 2016 Accepted: February 21, 2017 Published: March 03, 2017 ABSTRACT MNS16A, a functional polymorphic tandem repeat minisatellite, is located in the promoter region of an antisense transcript of the human telomerase reverse transcriptase gene. MNS16A promoter activity depends on the variable number of tandem repeats (VNTR) presenting varying numbers of transcription factor binding sites for GATA binding protein 1. Although MNS16A has been investigated in multiple cancer epidemiology studies with incongruent findings, functional data of only two VNTRs (VNTR-243 and VNTR-302) were available thus far, linking the shorter VNTR to higher promoter activity. For the first time, we investigated promoter activity of all six VNTRs of MNS16A in cell lines of colorectal, lung and prostate cancer using Luciferase reporter assay. In all investigated cell lines shorter VNTRs showed higher promoter activity. While this anticipated indirect linear relationship was affirmed for colorectal cancer SW480 ( P = 0.006), a piecewise linear regression model provided significantly better model fit in lung cancer A-427 ( P = 6.9 × 10 –9 ) and prostate cancer LNCaP ( P = 0.039). In silico search for transcription factor binding sites in MNS16A core repeat element suggested a higher degree of complexity involving X-box binding protein 1, general transcription factor II–I, and glucocorticoid receptor alpha in addition to GATA binding protein 1. Further functional studies in additional cancers are requested to extend our knowledge of MNS16A functionality uncovering potential cancer type-specific differences. Risk alleles may vary in different malignancies and their determination in vitro could be relevant for interpretation of genotype data. |
| Databáze: | OpenAIRE |
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