小脑变性相关 (CDR) 蛋白与副肿瘤性小脑变性 (PCD) 相关，这是一种罕见的神经退行性疾病，由肿瘤诱导的针对神经抗原的自身免疫引起，导致小脑中浦肯野神经元变性。 PCD 的发病机制尚不清楚，很大程度上是由于我们对 CDR 蛋白功能的了解有限。为此，我们对 CDR 敲除细胞进行了广泛的多组学分析，重点关注 CDR2L 蛋白，以更深入地了解 CDR 蛋白在卵巢癌中的特性。缺乏 CDR1、CDR2、使用RNA测序和基于质谱的蛋白质组学对CDR2L或CDR2L进行分析，以评估在没有这些蛋白质的情况下转录组、蛋白质组和分泌组的变化。对于每个敲除细胞系，我们鉴定了一组差异表达的基因和蛋白质。与 CDR1 和 CDR2 敲除细胞相比，CDR2L 敲除细胞显示出不同的表达谱。 CDR2L 的敲除导致参与核糖体生物发生、蛋白质翻译和细胞周期进展的基因失调，最终导致体外细胞增殖受损。其中一些基因在转录水平上同时上调，在蛋白质水平上下调。我们的研究首次对 CDR 基因敲除的影响进行了综合多组学分析，为 CDR 的生物学特性提供了新的见解。卵巢癌中的蛋白质，也是未来研究 CDR 蛋白质的宝贵资源。© 2024。作者。

Cerebellar degeneration-related (CDR) proteins are associated with paraneoplastic cerebellar degeneration (PCD) - a rare, neurodegenerative disease caused by tumour-induced autoimmunity against neural antigens resulting in degeneration of Purkinje neurons in the cerebellum. The pathogenesis of PCD is unknown, in large part due to our limited understanding of the functions of CDR proteins. To this end, we performed an extensive, multi-omics analysis of CDR-knockout cells focusing on the CDR2L protein, to gain a deeper understanding of the properties of the CDR proteins in ovarian cancer.Ovarian cancer cell lines lacking either CDR1, CDR2, or CDR2L were analysed using RNA sequencing and mass spectrometry-based proteomics to assess changes to the transcriptome, proteome and secretome in the absence of these proteins.For each knockout cell line, we identified sets of differentially expressed genes and proteins. CDR2L-knockout cells displayed a distinct expression profile compared to CDR1- and CDR2-knockout cells. Knockout of CDR2L caused dysregulation of genes involved in ribosome biogenesis, protein translation, and cell cycle progression, ultimately causing impaired cell proliferation in vitro. Several of these genes showed a concurrent upregulation at the transcript level and downregulation at the protein level.Our study provides the first integrative multi-omics analysis of the impact of knockout of the CDR genes, providing both new insights into the biological properties of the CDR proteins in ovarian cancer, and a valuable resource for future investigations into the CDR proteins.© 2024. The Author(s).