Single-cell analysis of a high-grade serous ovarian cancer cell line reveals transcriptomic changes and cell subpopulations sensitive to epigenetic combination treatment

PLOS ONE(2022)

引用 2|浏览1
暂无评分
摘要
Ovarian cancer (OC) is a lethal gynecological malignancy with a five-year survival rate of only 46%. Development of resistance to platinum-based chemotherapy is a common cause of high mortality rates among OC patients. Tumor and transcriptomic heterogeneity are drivers of platinum resistance in OC. Platinum-based chemotherapy enriches for ovarian cancer stem cells (OCSCs) that are chemoresistant and contribute to disease recurrence and relapse. Studies examining the effect of different treatments on subpopulations of HGSOC cell lines are limited. Having previously demonstrated that combined treatment with an enhancer of zeste homolog 2 inhibitor (EZH2i) and a RAC1 GTPase inhibitor (RAC1i) inhibited survival of OCSCs, we investigated EZH2i and RAC1i combination effects on HGSOC heterogeneity using single cell RNA sequencing. We demonstrated that RAC1i reduced expression of stemness and early secretory marker genes, increased expression of an intermediate secretory marker gene and induced inflammatory gene expression. Importantly, RAC1i alone and in combination with EZH2i significantly reduced oxidative phosphorylation and upregulated Sirtuin signaling pathways. Altogether, we demonstrated that combining a RAC1i with an EZH2i promoted differentiation of subpopulations of HGSOC cells, supporting the future development of epigenetic drug combinations as therapeutic approaches in OC.
更多
查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要