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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2023.6
- 수록면
- 347 - 352 (6page)
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The protein family of poly (ADP-ribose) polymerases (PARPs) iscomprised of multifunctional nuclear enzymes. Several PARPinhibitors have been developed as new anticancer drugs tocombat resistance to chemotherapy. Herein, we characterizedPARP4 mRNA expression profiles in cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines. PARP4 mRNA expressionwas significantly upregulated in cisplatin-resistant ovariancancer cell lines, and this upregulation was associated with thehypomethylation of specific cytosine-phosphate-guanine (CpG)sites (cg18582260 and cg17117459) on its promoter. ReducedPARP4 expression was restored by treating cisplatin-sensitive celllines with a demethylation agent, implicating the epigenetic regulationof PARP4 expression by promoter methylation. Depletionof PARP4 expression in cisplatin-resistant cell lines reducedcisplatin chemoresistance and promoted cisplatin-induced DNAfragmentation. The differential mRNA expression and DNA methylationstatus at specific PARP4 promoter CpG sites (cg18582260and cg17117459) according to cisplatin responses, was furthervalidated in primary ovarian tumor tissues. The results showedsignificantly increased PARP4 mRNA expressions and decreasedDNA methylation levels at specific PARP4 promoter CpG sites(cg18582260 and cg17117459) in cisplatin-resistant patients.
Additionally, the DNA methylation status at cg18582260 CpGsites in ovarian tumor tissues showed fairly clear discriminationbetween cisplatin-resistant patients and cisplatin-sensitive patients,with high accuracy (area under the curve = 0.86, P = 0.003845).
Our findings suggest that the DNA methylation status of PARP4at the specific promoter site (cg18582260) may be a useful diagnosticbiomarker for predicting the response to cisplatin in ovariancancer patients.
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