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RNFT2沉默通过mTORC1信号通路抑制胃癌细胞的增殖和迁移。

Silencing of RNFT2 suppresses cell proliferation and migration through mTORC1 signaling pathway in gastric cancer.

作者信息

Wang Younan, Ma Qianyun, Zhu Zeyu, Sang Huaiming, Fan Hao, Li Zhipeng

机构信息

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.

出版信息

Amino Acids. 2025 Mar 18;57(1):19. doi: 10.1007/s00726-025-03449-2.

DOI:10.1007/s00726-025-03449-2
PMID:40097779
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11913916/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4564/11913916/d400c117928c/726_2025_3449_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4564/11913916/2a554d33f028/726_2025_3449_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4564/11913916/ebbd77036a86/726_2025_3449_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4564/11913916/e4e7a6f39e28/726_2025_3449_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4564/11913916/09e2a0ff7781/726_2025_3449_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4564/11913916/f9a2b1ce1770/726_2025_3449_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4564/11913916/d400c117928c/726_2025_3449_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4564/11913916/2a554d33f028/726_2025_3449_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4564/11913916/ebbd77036a86/726_2025_3449_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4564/11913916/e4e7a6f39e28/726_2025_3449_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4564/11913916/09e2a0ff7781/726_2025_3449_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4564/11913916/f9a2b1ce1770/726_2025_3449_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4564/11913916/d400c117928c/726_2025_3449_Fig6_HTML.jpg

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本文引用的文献

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SMYD5 methylation of rpL40 links ribosomal output to gastric cancer.SMYD5 对 rpL40 的甲基化将核糖体的输出与胃癌联系起来。
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KLHL21 suppresses gastric tumourigenesis via maintaining STAT3 signalling equilibrium in stomach homoeostasis.KLHL21 通过维持胃稳态中的 STAT3 信号平衡抑制胃肿瘤发生。
Gut. 2024 Oct 7;73(11):1785-1798. doi: 10.1136/gutjnl-2023-331111.
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mTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis.
mTORC1 信号在脑内皮祖细胞中的作用促进 CCM 发病机制。
Circ Res. 2024 Aug 2;135(4):e94-e113. doi: 10.1161/CIRCRESAHA.123.324015. Epub 2024 Jul 3.
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Robotic versus laparoscopic distal gastrectomy for resectable gastric cancer: a randomized phase 2 trial.机器人与腹腔镜远端胃切除术治疗可切除性胃癌:一项随机 2 期试验。
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Effects of RAD50 SNP, sodium intake, and H. pylori infection on gastric cancer survival in Korea.RAD50 单核苷酸多态性、钠摄入量和 H. pylori 感染对韩国胃癌生存的影响。
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