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

The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
Ye-Na HaJung-Hyuck Ahn

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 α-Nacetylgalactosaminidase (NAGA) as one of the key candidate genes for cisplatin drug response. Interestingly, in cisplatin-resistant cell lines, NAGA was significantly downregulated 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 N...Continue Reading

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Citations

Mar 5, 2019·International Journal of Gynaecology and Obstetrics : the Official Organ of the International Federation of Gynaecology and Obstetrics·Janhvi SookramOlga Ostrovsky
Jun 13, 2019·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Alberta L WangKelan G Tantisira
Aug 28, 2020·Frontiers in Oncology·Susana Romero-GarciaAngeles Carlos-Reyes
Jul 21, 2021·Pharmacogenomics·Yuselin MoraPriscilla Brebi

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Methods Mentioned

BETA
MDAH
PCR
transfection
electrophoresis
methylation profiling

Software Mentioned

Image
GraphPad Prism5
Image J
GraphPad
Bioconductor “ affy ”

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