Details

Autor(en) / Beteiligte

• He, Wanhong
• Zhu, Haijun
• Zhang, Sufen
• Shu, Guang
• Lei, Han
• Wang, Maonan
• Yin, Gang
• Ni, Xiaohua
• Wu, Qihan

Titel

Epigenetic editing of BRCA1 promoter increases cisplatin and olaparib sensitivity of ovarian cancer cells

Ist Teil von

• Epigenetics, 2024-12, Vol.19 (1), p.2357518-2357518

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Taylor & Francis Journals Auto-Holdings Collection

Beschreibungen/Notizen

• Drug resistance is the primary contributor to the high mortality rate of ovarian cancer (OC). The loss of /2 function is linked to drug sensitivity in OC cells. The aim of this study is to enhance the drug sensitivity of OC cells by inducing dysfunction through promoter epigenetic editing. Epigenetic regulatory regions within the promoter, affecting gene expression, were initially discerned through analysis of clinical samples. Subsequently, we designed and rigorously validated epigenetic editing tools. Ultimately, we evaluated the cisplatin and olaparib sensitivity of the OC cells after editing. The promoter contains two CpG-rich regions, with methylation of the region covering the transcription start site (TSS) strongly correlating with transcription and influencing OC development, prognosis, and homologous recombination (HR) defects. Targeting this region in OC cells using our designed epigenetic editing tools led to substantial and persistent DNA methylation changes, accompanied by significant reductions in H3K27ac histone modifications. This resulted in a notable suppression of expression and a decrease in HR repair capacity. Consequently, edited OC cells exhibited heightened sensitivity to cisplatin and olaparib, leading to increased apoptosis rates. Epigenetic inactivation of the promoter can enhance cisplatin and olaparib sensitivity of OC cells through a reduction in HR repair capacity, indicating the potential utility of epigenetic editing technology in sensitization therapy for OC.