Abstract:
Ovarian cancer represents a major public health concern worldwide. High-grade serous ovarian cancer (HGSOC) is a primary epithelial ovarian cancer. Cisplatin resistance poses a substantial obstacle in the management of HGSOC, leading to unfavourable patient outcomes. The primary objective of this study was to investigate the mechanisms underlying cisplatin resistance in patients with HGSOC. TCGA data, GSE65819 dataset, and multiMiR package were used to identify 35 differentially expressed miRNAs (DE-miRNAs). Differentially expressed mRNAs (DE-mRNAs) are indicated using TCGA data. Further, weighted gene co-expression network analysis (WGCNA) was used to determine the correlation coefficients between the DE-mRNAs and DE-miRNAs. A network of miR-486-3p and TMIGD2 was constructed. Molecular biology experiments also indicated that low miR-486-3p or high TMIGD2 expression significantly increased the migratory rate and cisplatin resistance of both SK-OV3 and A2780 cells. In contrast, overexpression of miR-486-3p or downregulation of TMIGD2 decreased the migration rate and enhanced the sensitivity to cisplatin treatment, which provides insights for the development of novel therapeutic approaches. Moreover, RNA-binding protein immunoprecipitation experiment was used to determine the relationship between miR-486-3p and TMIGD2. Cell rescue assays were performed to further investigate these regulatory relationships. In TCGA and GSE65819 datasets, Benjamini and Hochberg false discovery rates (FDR) were selected for P-values. In the molecular biology experiments, one-way analysis of variance was employed to compare different groups, supplemented by Bonferroni post-hoc testing. Statistical significance was set at p < 0.05.
摘要:
卵巢癌是世界范围内主要的公共卫生问题。高级别浆液性卵巢癌(HGSOC)是原发性上皮性卵巢癌。顺铂耐药在HGSOC的管理中构成了实质性障碍,导致不利的患者结果。这项研究的主要目的是研究HGSOC患者顺铂耐药的潜在机制。TCGA数据,GSE65819数据集,和multiMiR包装用于鉴定35种差异表达的miRNA(DE-miRNA)。使用TCGA数据指示差异表达的mRNA(DE-mRNA)。Further,加权基因共表达网络分析(WGCNA)用于确定DE-mRNA和DE-miRNA之间的相关系数。构建了miR-486-3p和TMIGD2的网络。分子生物学实验还表明,低miR-486-3p或高TMIGD2表达均显着增加SK-OV3和A2780细胞的迁徙率和顺铂抗性。相比之下,miR-486-3p的过表达或TMIGD2的下调降低了迁移率并增强了对顺铂治疗的敏感性,这为开发新的治疗方法提供了见解。此外,RNA结合蛋白免疫沉淀实验用于确定miR-486-3p与TMIGD2之间的关系。进行细胞拯救测定以进一步研究这些调节关系。在TCGA和GSE65819数据集中,选择Benjamini和Hochberg错误发现率(FDR)作为P值。在分子生物学实验中,采用单向方差分析比较不同的组,由Bonferroni事后测试补充。统计学显著性设定为p<0.05。