DNA甲基化、组蛋白修饰和miRNAs对卵巢癌（OC）的进展和治疗反应具有影响。鉴定在耐药OC细胞系中表观遗传下调的miRNAs，这些miRNAs可能在耐药和/或药物诱导的间质样表型中发挥作用。对亲本和卡铂耐药OC细胞MES-OV和MES-OV CBP进行miRNA分析。采用RT-qPCR验证，表观修饰调制和其他CBP耐药OC细胞系选择相关的miRNAs。将miRNA预测的靶基因与差异表达基因（DEGs）、通路和功能分析结合使用以预测它们的生物学作用。进行数据挖掘以确定它们可能的预后和预测价值。miRNA分析揭示OC细胞中存在48个下调的miRNAs，它们的药物敏感性和转移潜力受到表观遗传调控因子的影响。从选定的14个miRNAs中，经验证有9个发生了变化，其中7个在经历表观修饰抑制剂治疗后恢复了表达。只有3个miRNAs在其他OC细胞系中具有相似的表达模式。miRNA-mRNA的整合分析得到了56个靶基因。通路分析揭示这些基因参与细胞黏附、迁移和侵袭。功能分析确认了miR-103a-3p、miR-17-5p和miR-107在细胞侵袭中的作用，而数据挖掘则显示了它们的预后和预测价值。只有miR-103a-3p在构成性水平上受到表观遗传调控。高通量miRNA和cDNA分析结合通路分析和数据挖掘提供了证据，表明miRNAs可以在耐药的间质样OC细胞中被表观遗传调控，这些miRNAs可能是用于对抗治疗诱导的短期总生存及肿瘤转移潜力的标志物。版权所有©2023作者。Elsevier Masson SAS发布。保留所有权利。

DNA methylation, histone modifications, and miRNAs affect ovarian cancer (OC) progression and therapy response.Identification of epigenetically downregulated miRNAs in drug-resistant OC cell lines with a possible role in drug resistance and/or drug-induced mesenchymal-like phenotype.MiRNA profiling was performed on parental and carboplatin-resistant OC cells, MES-OV and MES-OV CBP. RT-qPCR validation, epigenetic modulation and other CBP-resistant OC cell lines were used to select miRNAs of interest. The integration of miRNA-predicted target genes and differentially expressed genes (DEGs), pathway and functional analysis were used for forecasting their biological role. Data mining was performed to determine their possible prognostic and predictive values.MiRNA profiling revealed 48 downregulated miRNAs in OC cells whose drug sensitivity and metastatic potential were impacted by epigenetic modulators. Of the fourteen selected, nine were validated as changed, and seven of these restored their expression upon treatment with epigenetic inhibitors. Only three had similar expression patterns in other OC cell lines. MiRNA-mRNA integrative analysis resulted in 56 target DEGs. Pathway analysis revealed that these genes are involved in cell adhesion, migration, and invasion. The functional analysis confirmed the role of miR-103a-3p, miR-17-5p and miR-107 in cell invasion, while data mining showed their prognostic and predictive values. Only miR-103a-3p was epigenetically regulated at the constitutive level.High throughput miRNA and cDNA profiling coupled with pathway analysis and data mining delivered evidence for miRNAs which can be epigenetically regulated in drug-resistant, mesenchymal-like OC cells as possible markers to combat therapy-induced short overall survival and tumor metastatic potential.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.