Gao Xia, Zhang Xiuqin, Huang Junjie, Tan Zhenyu, Yang Jing, Yuan Liuhong, Wang Pengjun, Chen Feier, Wu Huiyan, Feng Changyi, Yu Hong, Bao Shisan, Fu Da, Tao Kun
Department of Pathology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
J Cancer. 2025 Jul 4;16(10):3080-3093. doi: 10.7150/jca.111459. eCollection 2025.
RNA-binding motif protein-10 (RBM10) plays a role in pancreatic adenocarcinoma (PAAD), though its precise underlying mechanism remains unclear. The current study investigates the role of RBM10 in pancreatic cancer progression and immune regulation. RBM10 expression in pancreatic tissues from PAAD patient was assessed using Western blotting, RT-qPCR, and immunohistochemistry, revealing lower levels in pancreatic cancerous tissues compared to adjacent non-cancerous tissues. This finding aligns with experiments where RBM10 knockdown in pancreatic cancer cells enhanced colony formation, migration, and proliferation, which correlated with increased P-JAK1, P‑JAK2, and P-STAT3 levels. Bioinformatics identified RBM10-related pathways and immune changes. Moreover, RBM10 deficiency in cancer cells increased PD-1 expression in natural killer cells , reducing their tumour-killing ability. However, treatment with the JAK pathway inhibitor AZD1480 restored NK cell cytotoxicity against cancer cells. Finally, high RBM10 expression was associated with a favourable prognosis in pancreatic cancer patients, suggesting that RBM10 inhibits pancreatic cancer progression by suppressing tumour immune escape through JAK-STAT-mediated regulation of PD-1 expression in NK cells. This finding offers potential for the development of novel precision-targeted therapies in the management of pancreatic cancer.
RNA结合基序蛋白10（RBM10）在胰腺腺癌（PAAD）中发挥作用，但其确切的潜在机制仍不清楚。本研究调查了RBM10在胰腺癌进展和免疫调节中的作用。使用蛋白质免疫印迹法、逆转录定量聚合酶链反应（RT-qPCR）和免疫组织化学评估了PAAD患者胰腺组织中RBM10的表达，结果显示癌组织中的水平低于相邻的非癌组织。这一发现与胰腺癌细胞中RBM10基因敲低增强集落形成、迁移和增殖的实验结果一致，这与磷酸化JAK1（P-JAK1）、磷酸化JAK2（P-JAK2）和磷酸化信号转导和转录激活因子3（P-STAT3）水平升高相关。生物信息学确定了与RBM10相关的信号通路和免疫变化。此外，癌细胞中RBM10的缺乏增加了自然杀伤细胞中程序性死亡受体1（PD-1）的表达，降低了它们的肿瘤杀伤能力。然而，用JAK信号通路抑制剂AZD1480治疗可恢复自然杀伤细胞对癌细胞的细胞毒性。最后，RBM10高表达与胰腺癌患者的良好预后相关，这表明RBM10通过JAK-STAT介导的自然杀伤细胞中PD-1表达调控抑制肿瘤免疫逃逸，从而抑制胰腺癌进展。这一发现为开发新型精准靶向治疗胰腺癌提供了可能性。
