Zhang Nailin, Yan Lina, Cao Hua, Zhang Nana, Zhang Tong, Guan Shengjiang, Liu Qiquan
Department of Spleen and Stomach Diseases, Hebei Provincial Hospital of Chinese Medicine, Shijiazhuang, 050000, China.
Department of Spleen and Stomach Diseases, Hebei Key Laboratory of Turbidity Toxin Syndrome, Hebei University of Chinese Medicine, Shijiazhuang, 050000, China.
Sci Rep. 2025 Jul 1;15(1):21294. doi: 10.1038/s41598-025-01125-9.
Gastric cancer (GC) is one of the most common malignancies worldwide, and its development is closely associated with the abnormal expression of numerous genes. RNA - binding protein with multiple splicing 2 (RBPMS2), a member of the RNA - binding protein family, has recently been found to be abnormally activated in GC cells. Meanwhile, pyroptosis, a form of programmed cell death, is related to tumorigenesis, development, and immune responses.This study investigated the role of the RNA - binding protein RBPMS2 in GC. It revealed the high expression of RBPMS2 in GC cells and its association with poor prognosis. RBPMS2 promoted the proliferation, invasion, and migration of GC cells while inhibiting pyroptosis by suppressing the NLR family pyrin domain containing 3 (NLRP3)/caspase - 1/gasdermin (DGSDMD) signaling pathway. Knocking out RBPMS2 activated pyroptosis, leading to cell membrane damage and increased expression of pyroptosis - related proteins. The NLRP3 inhibitor MCC950 reversed these effects, confirming the involvement of this pathway. These findings suggest that RBPMS2 may be a potential therapeutic target for inducing pyroptosis in gastric cancer cells, providing novel insights into treatment strategies for gastric cancer.
胃癌(GC)是全球最常见的恶性肿瘤之一,其发展与众多基因的异常表达密切相关。具有多个剪接位点的RNA结合蛋白2(RBPMS2)是RNA结合蛋白家族的成员之一,最近被发现在GC细胞中异常激活。同时,细胞焦亡作为一种程序性细胞死亡形式,与肿瘤发生、发展及免疫反应相关。本研究探讨了RNA结合蛋白RBPMS2在GC中的作用。研究揭示了RBPMS2在GC细胞中的高表达及其与不良预后的关联。RBPMS2通过抑制含NLR家族pyrin结构域蛋白3(NLRP3)/半胱天冬酶-1/ Gasdermin(DGSDMD)信号通路促进GC细胞的增殖、侵袭和迁移,同时抑制细胞焦亡。敲除RBPMS2可激活细胞焦亡,导致细胞膜损伤并增加细胞焦亡相关蛋白的表达。NLRP3抑制剂MCC950可逆转这些效应,证实了该信号通路的参与。这些发现表明,RBPMS2可能是诱导胃癌细胞发生细胞焦亡的潜在治疗靶点,为胃癌治疗策略提供了新的见解。