RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
囊泡介导运输相关基因 SEC23A 通过调控细胞周期促进细胞增殖，从而导致胃癌进展
英文原题：Vesicle-mediated transport-related gene SEC23A promotes cell proliferation by regulating cell cycle leading to gastric cancer progression.
查看英文原题
Vesicle-mediated transport-related gene SEC23A promotes cell proliferation by regulating cell cycle leading to gastric cancer progression.
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中文摘要
胃癌（GC）是一种高发病率且致死性强的胃肠道肿瘤。囊泡介导转运相关基因（VMTRGs）的失调与肿瘤发生和疾病进展密切相关。
然而，VMTRGs在GC中的预后价值尚不清楚。在本研究中，基于我们的蛋白质组学数据和公共数据库，我们鉴定了经Ming分型确定的具有更多转移和复发的浸润型GC中差异表达的VMTRGs。最小绝对收缩和选择算子（LASSO）回归从41个浸润相关VMTRGs中鉴定出3个VMTRGs（SEC23A、RAB31和GABARAPL2），基于此构建了风险模型囊泡-浸润Lasso系统（VILS），并通过免疫微环境分析和功能富集分析验证了其有效性和潜在重要性。作为GC的独立预后因素，VILS与其他临床独立预后因素结合形成列线图，能够有效预测GC预后。VILS高风险组具有更高的M2巨噬细胞和癌相关成纤维细胞浸润，以及更低的Th1细胞和NK 细胞浸润。SEC23A在GC组织和细胞中高表达。通过体外实验包括集落形成实验和CCK-8实验，以及使用皮下异种移植小鼠模型的体内实验，评估了SEC23A在GC细胞中的重要性。
结果表明，SEC23A在体外和体内通过调控细胞周期促进GC细胞增殖和肿瘤生长。VILS为GC患者提供了优异的预后预测，并与抗肿瘤免疫细胞浸润相关。SEC23A作为VILS的优势基因，在GC中高表达，并通过多种分子机制促进GC生长和恶性进展。
我们的研究首次揭示了SEC23A对胃癌细胞增殖的影响。因此，SEC23A有潜力成为GC诊断和治疗的新靶点。
展开英文摘要原文
Gastric cancer (GC) is a highly prevalent and lethal gastrointestinal cancer. Dysregulation of vesicle-mediated transport-related genes (VMTRGs) is closely associated with tumorigenesis and disease progression.
However, the prognostic value of VMTRGs in GC remains unclear. In this study, on the basis of our proteomics data and public databases, we identify differentially expressed VMTRGs in infiltrative-type GC with more metastases and recurrences identified by Ming's classification. Least absolute shrinkage and selection operator (LASSO) regression identifies 3 VMTRGs ( SEC23A , RAB31 , and GABARAPL2 ) from 41 infiltrative-associated VMTRGs, based on which a risk model Vesicle-Infiltrative Lasso System (VILS) is constructed, and its effectiveness and potential importance are validated by immune microenvironment analysis and functional enrichment analysis. As an independent prognostic factor for GC, VILS, combined with other clinically independent prognostic factors to form a nomogram, is effective in predicting GC prognosis.
The VILS high-risk group has higher M2 macrophage and cancer-associated fibroblast infiltration, and lower infiltration of Th1 cells and natural killer cells. SEC23A is highly expressed in GC tissues and cells. The importance of SEC23A in GC cells is evaluated by in vitro assays including colony formation assay and CCK-8 assay, and by in vivo assay using a subcutaneous xenograft mouse model.
The results show that SEC23A promotes GC cell proliferation and tumor growth through regulation of the cell cycle in vitro and in vivo . VILS provides excellent prognostic prediction for GC patients and is correlated with antitumor immune cell infiltration. SEC23A , the dominant gene of VILS, is highly expressed in GC and promotes GC growth and malignant progression through various molecular mechanisms.
Our study reveals the effect of SEC23A on the proliferation of gastric cancer cells for the first time.
Therefore, SEC23A has the potential to be a new therapeutic target for the diagnosis and treatment of GC.
论文信息
- 作者
- Wang K、Rao S、Wei X、Xie W、Hong Z、Cheng J、Chen X、Hou J
- 单位
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361000, China.China
- 期刊
- Acta biochimica et biophysica Sinica2025 May 22
- 原文标识
- PubMed 40400443 · DOI 10.3724/abbs.2025051
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