突触融合蛋白 25 诱导的 MYC 上调促进高级别神经内分泌肺癌进展。

SNAP25-induced MYC upregulation promotes high-grade neuroendocrine lung carcinoma progression.

机构信息

The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.

Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Front Immunol. 2024 Oct 4;15:1411114. doi: 10.3389/fimmu.2024.1411114. eCollection 2024.

DOI:10.3389/fimmu.2024.1411114

PMID:39430761

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11486671/

Abstract

BACKGROUND

This study investigated the expression and role of Synaptosome associated protein 25 (SNAP25) in high-grade neuroendocrine carcinoma (HGNEC).

METHODS

We used differentially expressed analysis and weighted gene co-expression network analysis (WGCNA) to identify key genes and modules in HGNEC. KEGG and GO analyses helped understand these genes' roles, and ROC curves assessed their diagnostic value. We also studied SNAP25's relation to immune infiltration and confirmed findings with and vivo experiments and datasets.

RESULTS

WGCNA identified 595 key genes related to pathways like MAPK signaling, GABAergic synapse, and cancer-related transcriptional misregulation. Top genes included SNAP25, MYC, NRXN1, GAD2, and SYT1. SNAP25 was notably associated with M2 macrophage infiltration. Dataset GSE40275 confirmed SNAP25's high expression and poor prognosis in HGNEC. qRT-PCR and WB analyses showed increased SNAP25 and c-MYC levels in HGNEC, promoting MEK/ERK pathway activity. Reducing SNAP25 decreased H1299 cell proliferation, migration, invasion, and levels of c-MYC, MEK, and ERK. Finally, experiments further confirmed that SNAP25 knockout can inhibit tumor growth.

CONCLUSION

SNAP25 regulates c-MYC activation by stimulating the MEK/ERK pathway, ultimately influencing the development of HGNEC.

摘要

背景

本研究旨在探讨突触相关蛋白 25（SNAP25）在高级神经内分泌癌（HGNEC）中的表达和作用。

方法

我们采用差异表达分析和加权基因共表达网络分析（WGCNA）鉴定 HGNEC 中的关键基因和模块。KEGG 和 GO 分析有助于理解这些基因的作用，ROC 曲线评估其诊断价值。我们还研究了 SNAP25 与免疫浸润的关系，并通过体内外实验和数据集进行了验证。

结果

WGCNA 鉴定出 595 个与 MAPK 信号通路、γ-氨基丁酸能突触和癌症相关转录失调等途径相关的关键基因。重要基因包括 SNAP25、MYC、NRXN1、GAD2 和 SYT1。SNAP25 与 M2 巨噬细胞浸润显著相关。数据集 GSE40275 证实了 SNAP25 在 HGNEC 中高表达和预后不良。qRT-PCR 和 WB 分析显示 HGNEC 中 SNAP25 和 c-MYC 水平升高，促进 MEK/ERK 通路活性。降低 SNAP25 可降低 H1299 细胞增殖、迁移、侵袭和 c-MYC、MEK 和 ERK 水平。最后，体内实验进一步证实 SNAP25 敲除可抑制肿瘤生长。