Wang Younan, Ma Qianyun, Zhu Zeyu, Sang Huaiming, Fan Hao, Li Zhipeng
Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, Jiangsu Province, China.
Department of Gastroenterology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, 223300, Jiangsu Province, China.
Amino Acids. 2025 Mar 18;57(1):19. doi: 10.1007/s00726-025-03449-2.
Excellent biomarkers for predicting survival or therapeutic targets are still lacking in gastric cancer (GC), which is one of the most common causes of cancer-related death worldwide. Ring finger protein, transmembrane 2 (RNFT2), which has been reported to be involved in proteolytic process, but how it functions in tumors is rarely investigated. In the present study, we explored the biological property of RNFT2 in GC, we found that RNFT2 was significantly upregulated in GC, and could serve as a tumor marker to predict prognosis. A series of in vitro cell function experiments were performed, we found that knockdown of RNFT2 expression in GC cells could inhibit cell invasion, migration and proliferation. Besides, in vivo experiments also showed that silencing RNFT2 expression in gastric cancer cells significantly reduced tumor size. Furthermore, through gene set enrichment analysis (GSEA) and immunoblotting studies, we observed that RNFT2 might influence the proliferation, invasion and migration of GC cells through the mTORC1 signaling pathway. In summary, our results clarified the carcinogenic role of RNFT2 in GC progression, provided inspiration to further understand the molecular mechanism of GC and made RNFT2 as a potential target for GC diagnosis and therapy.
胃癌是全球癌症相关死亡的最常见原因之一,目前仍缺乏用于预测生存或治疗靶点的优秀生物标志物。据报道,环状指蛋白跨膜2(RNFT2)参与蛋白水解过程,但对其在肿瘤中的作用机制研究甚少。在本研究中,我们探究了RNFT2在胃癌中的生物学特性,发现RNFT2在胃癌中显著上调,并可作为预测预后的肿瘤标志物。我们进行了一系列体外细胞功能实验,发现敲低胃癌细胞中RNFT2的表达可抑制细胞侵袭、迁移和增殖。此外,体内实验还表明,沉默胃癌细胞中RNFT2的表达可显著减小肿瘤大小。此外,通过基因集富集分析(GSEA)和免疫印迹研究,我们观察到RNFT2可能通过mTORC1信号通路影响胃癌细胞的增殖、侵袭和迁移。总之,我们的研究结果阐明了RNFT2在胃癌进展中的致癌作用,为进一步了解胃癌的分子机制提供了思路,并使RNFT2成为胃癌诊断和治疗的潜在靶点。