癌细胞经历主要的表观遗传改变和转录组变化，包括组织和细胞类型特异性基因的异位表达。在这里，我们发现种系特异性 RNA 解旋酶 DDX4 在各种人类肿瘤中形成种芽颗粒样细胞质核糖核蛋白颗粒，但在培养的癌细胞中则不然。这些癌性 DDX4 复合物含有 RNA 结合蛋白和剪接调节因子，包括许多已知的胚芽颗粒成分。癌细胞中 DDX4 的缺失会引起转录组变化，并影响许多与癌症生长和侵袭有关的基因的选择性剪接景观，导致 DDX4 缺失癌细胞在免疫功能低下的小鼠中形成异种移植肿瘤的能力受损。重要的是，DDX4颗粒的出现与头颈鳞状细胞癌和较高组织学分级的前列腺癌患者的生存率较低有关。总而言之，这些结果表明，类似于胚芽颗粒的癌性 DDX4 颗粒控制基因表达并促进癌细胞的恶性和侵袭特性。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Cancer cells undergo major epigenetic alterations and transcriptomic changes, including ectopic expression of tissue- and cell-type-specific genes. Here, we show that the germline-specific RNA helicase DDX4 forms germ-granule-like cytoplasmic ribonucleoprotein granules in various human tumors, but not in cultured cancer cells. These cancerous DDX4 complexes contain RNA-binding proteins and splicing regulators, including many known germ granule components. The deletion of DDX4 in cancer cells induces transcriptomic changes and affects the alternative splicing landscape of a number of genes involved in cancer growth and invasiveness, leading to compromised capability of DDX4-null cancer cells to form xenograft tumors in immunocompromised mice. Importantly, the occurrence of DDX4 granules is associated with poor survival in patients with head and neck squamous cell carcinoma and higher histological grade of prostate cancer. Taken together, these results show that the germ-granule-resembling cancerous DDX4 granules control gene expression and promote malignant and invasive properties of cancer cells.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.