Overexpression of methylation-driven DCC suppresses proliferation of lung cancer cells
Journal
Translational Cancer Research
Journal Volume
5
Journal Issue
2
Pages
169-175
Date Issued
2016
Author(s)
Abstract
Background: DNA methylation is an epigenetic marker associated with regulation of gene expression and gene silencing. The active role of DNA methylation has been thoroughly studied in a number of cancer types. The deleted in colorectal carcinoma (DCC) gene, located at chromosome 18q21, plays an important role as a tumor suppressor and is associated with hypermethylation in head and neck squamous cell carcinoma. However, the methylation patterns and functional significance of DCC in lung cancer are still not known. Methods: RT-PCR was used to examine the endogenous expression levels of DCC in two lung cancer cell lines (A549, H1299) and their normal counterpart (Beas-2B). The demethylating agent, 5-aza-2'- deoxycytidine (5-aza), was used to examine the role of methylation in regulating expression of DCC in lung cancer cell lines. DCC was also overexpressed to evaluate its role in proliferation and colony formation. Finally, the gene expression signature of public dataset GSE68456 was used to elucidate the prognostic roles of DCC in lung adenocarcinoma patients. Results: Endogenous expression of DCC was significantly decreased in lung cancer compared to the normal cells (P < 0.0001). Furthermore, treatment with 10 μM 5-aza significantly up-regulated DCC in cancer cell lines (P?0.001), but not in Beas-2B cells. Overexpression of DCC significantly decreased cell proliferation (P < 0.05) and colony formation (P?0.001). Finally, significantly lower survival rates (P < 0.001) were observed when expression levels of DCC were decreased. Conclusions: Our results indicate that DCC is regulated by methylation in lung cancer cell lines, and may be associated with cell proliferation, colony formation, and prognoses of lung cancer in patients. ? Translational Cancer Research. All rights reserved.
SDGs
Publisher
AME Publishing Company
Type
journal article