DDX41 inhibits cancer cell proliferation and regulates immune response expression

DDX41, a member of the DEXDc family of helicases and an innate immune protein, senses cytosolic DNA and bacterial secondary messengers and initiates signaling via the adaptor STING to induce type 1 interferon (IFN) response in dendritic cells. However, DDX41 function in tumor progression is poorly understood. Here we found that the DDX41 inhibited proliferation and promoted apoptosis, reported the whole transcriptome profiling in HeLa cells. RNA-seq analyses revealed that the overexpression of DDX41 resulted in 959 genes being differentially expressed (504 up-regulated and 455 down-regulated) compared to the control in HeLa cells. Interestingly, functional clustering pathway enrichment analysis of transcription identified antigen processing and presentation pathways were significantly activated in DDX41 overexpression samples, but alternative splicing enriched in the epidermal growth factor receptor signaling pathway and fibroblast growth factor receptor signaling pathway. The five antigen processing and processing genes, which could regulate cross-presentation of antigens and protective antitumor immune responses, were significantly upregulated, suggesting DDX41 is the key player in tumor immunity. In conclusion, our RNA-seq data identified molecules and pathways involved in the mechanisms of DDX41 that adds to the understanding of critical DDX41 tumorigenesis functions. transcrptional analysis of DDX41 overexpression and control in Hela cells

DDX41是DEXDc解旋酶家族成员，亦是一种先天免疫蛋白，可识别胞质DNA与细菌第二信使，并通过接头蛋白STING（Stimulator of Interferon Genes）启动信号通路，在树突状细胞中诱导I型干扰素（IFN）应答。然而，学界对于DDX41在肿瘤进展中的功能尚不甚明确。本研究发现DDX41可抑制细胞增殖并促进细胞凋亡，并完成了HeLa细胞的全转录组图谱分析并予以报道。RNA测序（RNA-seq）分析显示，相较于对照组，HeLa细胞中DDX41过表达导致959个基因出现差异表达，其中504个基因上调、455个基因下调。有趣的是，对转录组数据进行功能聚类通路富集分析后发现，DDX41过表达样本中抗原加工与提呈通路显著激活；而可变剪接相关通路则富集于表皮生长因子受体信号通路与成纤维细胞生长因子受体信号通路。五个可调控抗原交叉提呈与保护性抗肿瘤免疫应答的抗原加工相关基因出现显著上调，这提示DDX41是肿瘤免疫中的关键调控因子。综上，本研究的RNA-seq数据鉴定出了参与DDX41作用机制的相关分子与通路，为深化对DDX41肿瘤发生关键功能的认知提供了新的依据。本数据集包含HeLa细胞中DDX41过表达组与对照组的转录组分析数据。