Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Oncol Rep. 2021 Mar;45(3):1213-1225. doi: 10.3892/or.2021.7951. Epub 2021 Jan 25.
DEAD‑box helicase 41 (DDX41) is an RNA helicase and accumulating evidence has suggested that DDX41 is involved in pre‑mRNA splicing during tumor development. However, the role of DDX41 in tumorigenesis remains unclear. In order to determine the function of DDX41, the human DDX41 gene was cloned and overexpressed in HeLa cells. The present study demonstrated that DDX41 overexpression inhibited proliferation and promoted apoptosis in HeLa cells. RNA‑sequencing analysis of the transcriptomes in overexpressed and normal control samples. DDX41 regulated 959 differentially expressed genes compared with control cells. Expression levels of certain oncogenes were also regulated by DDX41. DDX41 selectively regulated the alternative splicing of genes in cancer‑associated pathways including the EGFR and FGFR signaling pathways. DDX41 selectively upregulated the expression levels of five antigen processing and presentation genes (HSPA1A, HSPA1B, HSPA6, HLA‑DMB and HLA‑G) and downregulated other immune‑response genes in HeLa cells. Additionally, DDX41‑regulated oncogenes and antigen processing and presentation genes were associated with patient survival rates. Moreover, DDX41 expression was associated with immune infiltration in cervical and endocervical squamous cancer. The present findings showed that DDX41 regulated the cancer cell transcriptome at both the transcriptional and alternative splicing levels. The DDX41 regulatory network predicted the biological function of DDX41 in suppressing tumor cell growth and regulating cancer immunity, which may be important for developing anticancer therapeutics.
DEAD- box 解旋酶 41 (DDX41) 是一种 RNA 解旋酶，越来越多的证据表明，DDX41 参与肿瘤发展过程中的前体 mRNA 剪接。然而，DDX41 在肿瘤发生中的作用尚不清楚。为了确定 DDX41 的功能，本研究将人 DDX41 基因克隆并在 HeLa 细胞中过表达。本研究表明，DDX41 过表达抑制了 HeLa 细胞的增殖并促进了细胞凋亡。对过表达和正常对照样本的转录组进行 RNA 测序分析。与对照细胞相比，DDX41 调节了 959 个差异表达基因。某些癌基因的表达水平也受到 DDX41 的调节。DDX41 选择性地调节了包括 EGFR 和 FGFR 信号通路在内的癌症相关途径中基因的可变剪接。DDX41 选择性地上调了 5 个抗原加工和呈递基因（HSPA1A、HSPA1B、HSPA6、HLA-DMB 和 HLA-G）的表达水平，并下调了 HeLa 细胞中其他免疫反应基因的表达水平。此外，DDX41 调节的癌基因和抗原加工和呈递基因与患者的生存率相关。此外，DDX41 表达与宫颈和宫颈内腺癌的免疫浸润相关。本研究结果表明，DDX41 在上转录和可变剪接水平上调节癌细胞的转录组。DDX41 调控网络预测了 DDX41 在抑制肿瘤细胞生长和调节肿瘤免疫中的生物学功能，这对于开发抗癌治疗药物可能很重要。
