DNA Methylation Transcriptionally Regulates the Putative Tumor Cell Growth Suppressor ZNF677 in Non-small Cell Lung Cancers

Overview

Journal Oncotarget

Specialty Oncology

Date 2014 Dec 16

PMID 25504438

Citations 17

Authors

Gerwin Heller

Corinna Altenberger

Bianca Schmid

Maximilian Marhold

Erwin Tomasich

Barbara Ziegler

Leonhard Mullauer

Christoph Minichsdorfer

Gyorgy Lang

Adelheid End-Pfutzenreuter

Balazs Dome

Britt-Madeleine Arns

Kwun M Fong

Casey M Wright

Ian A Yang

Walter Klepetko

Christoph C Zielinski

Sabine Zochbauer-Muller

Affiliations

Soon will be listed here.

Abstract

In our study, we investigated the role of ZNF677 in non-small cell lung cancers (NSCLC). By comparing ZNF677 expression in primary tumor (TU) and in the majority of cases also of corresponding non-malignant lung tissue (NL) samples from > 1,000 NSCLC patients, we found tumor-specific downregulation of ZNF677 expression (adjusted p-values < 0.001). We identified methylation as main mechanism for ZNF677 downregulation in NSCLC cells and we observed tumor-specific ZNF677 methylation in NSCLC patients (p < 0.0001). In the majority of TUs, ZNF677 methylation was associated with loss of ZNF677 expression. Moreover, ZNF677 overexpression in NSCLC cells was associated with reduced cell proliferation and cell migration. ZNF677 was identified to regulate expression of many genes mainly involved in growth hormone regulation and interferon signalling. Finally, patients with ZNF677 methylated TUs had a shorter overall survival compared to patients with ZNF677 not methylated TUs (p = 0.013). Overall, our results demonstrate that ZNF677 is trancriptionally regulated by methylation in NSCLCs, suggest that ZNF677 has tumor cell growth suppressing properties in NSCLCs and that ZNF677 methylation might serve as prognostic parameter in these patients.

Citing Articles

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