Zhang Linteng, Zhang Lingyu, Li Qiumei, Fan Hongmei, Tao Shili, Wang Yang, Lin Juan, Ye Yunbin
Laboratory of Immuno-Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China; Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China.
The School of Basic Medical Sciences, Fujian Medical University, Xue Yuan Road, University Town, Fuzhou, Fujian 350122, China.
Gene. 2025 Sep 15;965:149682. doi: 10.1016/j.gene.2025.149682. Epub 2025 Jul 25.
Gastric cancer (GC) ranks among the most common and deadly malignancies globally. Small nuclear ribonucleoprotein polypeptide (SNRPB), a core spliceosomal component, was recently identified as essential for GC cell survival, although its mechanisms remain unclear. This study investigated the functions of SNRPB in GC progression and explored its underlying molecular mechanisms. SNRPB expression in GC tissues and adjacent non-cancerous tissues from 48 patients was analyzed via immunohistochemistry. SNRPB was significantly overexpressed in GC tissues compared with its expression in adjacent normal tissues, and higher SNRPB expression was associated with tumor stage and metastasis. Survival data obtained from the Kaplan-Meier Plotter website demonstrated that patients with GC and high SNRPB expression had a worse prognosis. Patient-derived organoids (PDOs) were successfully established from three patients with GC. These PDO models faithfully recapitulated the histological and genetic features of the original tumors. Notably, SNRPB knockdown in organoids significantly impaired organoid formation, demonstrating its essential role in maintaining tumor growth capacity. Complementary experiments in conventional 2D cultures illustrated that SNRPB knockdown reduced cell proliferation and migration. Mechanistically, transcriptomic analysis revealed that SNRPB silencing downregulated multiple genes involved in the extracellular matrix (ECM) receptor signaling pathway, thereby impairing tumor progression. In conclusion, our study identifies SNRPB as a key regulator of GC development through the ECM receptor signaling pathway, suggesting its potential as a therapeutic target.
胃癌（GC）是全球最常见且致命的恶性肿瘤之一。小核核糖核蛋白多肽（SNRPB）是剪接体的核心组成部分，最近被确定为对GC细胞存活至关重要，但其机制仍不清楚。本研究调查了SNRPB在GC进展中的作用，并探索了其潜在的分子机制。通过免疫组织化学分析了48例患者的GC组织和相邻非癌组织中SNRPB的表达。与相邻正常组织相比，SNRPB在GC组织中显著过表达，且较高的SNRPB表达与肿瘤分期和转移相关。从Kaplan-Meier Plotter网站获得的生存数据表明，GC且SNRPB高表达的患者预后较差。成功从三名GC患者中建立了患者来源的类器官（PDO）。这些PDO模型忠实地再现了原始肿瘤的组织学和遗传学特征。值得注意的是，类器官中SNRPB的敲低显著损害了类器官的形成，表明其在维持肿瘤生长能力中的重要作用。传统二维培养中的补充实验表明，SNRPB敲低减少了细胞增殖和迁移。机制上，转录组分析显示，SNRPB沉默下调了多个参与细胞外基质（ECM）受体信号通路的基因，从而损害肿瘤进展。总之，我们的研究通过ECM受体信号通路确定SNRPB是GC发展的关键调节因子，表明其作为治疗靶点的潜力。
