View : 42 Download: 0

Epigenetic modification of alpha-N-acetylgalactosaminidase enhances cisplatin resistance in ovarian cancer

Title
Epigenetic modification of alpha-N-acetylgalactosaminidase enhances cisplatin resistance in ovarian cancer
Authors
Ha, Ye-NaSung, Hye YounYang, San-DukChae, Yun JuJu, WoongAhn, Jung-Hyuck
Ewha Authors
주웅안정혁
SCOPUS Author ID
주웅scopus; 안정혁scopus
Issue Date
2018
Journal Title
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
ISSN
1226-4512JCR Link2093-3827JCR Link
Citation
vol. 22, no. 1, pp. 43 - 51
Keywords
Cisplatin resistanceDNA methylationOvarian canceralpha-N-acetylgalactosaminidase
Publisher
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
Indexed
SCIE; SCOPUS; KCI WOS
Abstract
Although cisplatin is one of the most effective antitumor drugs for ovarian cancer, the emergence of chemoresistance to cisplatin in over 80% of initially responsive patients is a major barrier to successful therapy. The precise mechanisms underlying the development of cisplatin resistance are not fully understood, but alteration of DNA methylation associated with aberrant gene silencing may play a role. To identify epigenetically regulated genes directly associated with ovarian cancer cisplatin resistance, we compared the expression and methylation profiles of cisplatin-sensitive and -resistant human ovarian cancer cell lines. We identified alpha-N-acetylgalactosaminidase (NAGA) as one of the key candidate genes for cisplatin drug response. Interestingly, in cisplatin-resistant cell lines, NAGA was significantly down-regulated and hypermethylated at a promoter CpG site at position +251 relative to the transcriptional start site. Low NAGA expression in cisplatin-resistant cell lines was restored by treatment with a DNA demethylation agent, indicating transcriptional silencing by hyper-DNA methylation. Furthermore, overexpression of NAGA in cisplatin-resistant lines induced cytotoxicity in response to cisplatin, whereas depletion of NAGA expression increased cisplatin chemoresistance, suggesting an essential role of NAGA in sensitizing ovarian cells to cisplatin. These findings indicate that NAGA acts as a cisplatin sensitizer and its gene silencing by hypermethylation confers resistance to cisplatin in ovarian cancer. Therefore, we suggest NAGA may be a promising potential therapeutic target for improvement of sensitivity to cisplatin in ovarian cancer.
DOI
10.4196/kjpp.2018.22.1.43
Appears in Collections:
의과대학 > 의학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE