Oncotarget

Research Papers:

MNS16A tandem repeat minisatellite of human telomerase gene: functional studies in colorectal, lung and prostate cancer

Philipp Hofer, Cornelia Zöchmeister, Christian Behm, Stefanie Brezina, Andreas Baierl, Angelina Doriguzzi, Vanita Vanas, Klaus Holzmann, Hedwig Sutterlüty-Fall and Andrea Gsur _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:28021-28027. https://doi.org/10.18632/oncotarget.15884

Metrics: PDF 1055 views  |   HTML 1445 views  |   ?  


Abstract

Philipp Hofer1, Cornelia Zöchmeister1, Christian Behm1, Stefanie Brezina1, Andreas Baierl2, Angelina Doriguzzi1, Vanita Vanas1, Klaus Holzmann1, Hedwig Sutterlüty-Fall1, Andrea Gsur1

1Medical University of Vienna, Institute of Cancer Research, A-1090 Vienna, Austria

2University 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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 15884