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上皮性卵巢癌中失调的 circRNAs 在临床前模型中的活性:靶标的鉴定和治疗干预的新方法。

Deregulated circRNAs in Epithelial Ovarian Cancer With Activity in Preclinical Models: Identification of Targets and New Modalities for Therapeutic Intervention.

机构信息

Roche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany;

Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland

出版信息

Cancer Genomics Proteomics. 2024 Apr 26;21(3):213-237. doi: 10.21873/cgp.20442.

Abstract

Epithelial ovarian cancer (EOC) is associated with a dismal prognosis due to development of resistance to chemotherapy and metastasis in the peritoneal cavity and distant organs. In order to identify new targets and treatment modalities we searched the literature for up- and and down-regulated circRNAs with efficacy in preclinical EOC-related in vivo systems. Our search yielded circRNAs falling into the following categories: cisplatin and paclitaxel resistance, transmembrane receptors, secreted factors, transcription factors, RNA splicing and processing factors, RAS pathway-related components, proteolysis and cell-cycle regulation, signaling-related proteins, and circRNAs regulating proteins in additional categories. These findings can be potentially translated by validation and manipulation of the corresponding targets, inhibition of circRNAs with antisense oligonucleotides (ASO), small interfering RNAs (siRNA) or small hairpin RNA (shRNA) or by reconstituting their activity.

摘要

上皮性卵巢癌 (EOC) 由于对化疗的耐药性以及在腹腔和远处器官中的转移而预后不良。为了确定新的靶点和治疗方法,我们在文献中搜索了在临床前 EOC 相关的体内系统中具有疗效的上调和下调的 circRNAs。我们的搜索结果分为以下几类:顺铂和紫杉醇耐药性、跨膜受体、分泌因子、转录因子、RNA 剪接和加工因子、RAS 通路相关成分、蛋白水解和细胞周期调控、信号相关蛋白以及调节其他类别蛋白的 circRNAs。这些发现可以通过验证和操作相应的靶点、使用反义寡核苷酸 (ASO)、小干扰 RNA (siRNA) 或短发夹 RNA (shRNA) 抑制 circRNAs 或重新构建其活性来潜在转化。

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