本研究探讨了突触体相关蛋白25（SNAP25）在高级别神经内分泌癌（HGNEC）中的表达和作用。我们使用差异表达分析和加权基因共表达网络分析（WGCNA）来识别HGNEC中的关键基因和模块。 KEGG 和 GO 分析有助于了解这些基因的作用，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，并通过体外和体内实验和数据集证实了这一发现。WGCNA 鉴定了 595 个与 MAPK 信号传导、GABA 能突触和癌症相关转录失调等途径相关的关键基因。排名靠前的基因包括 SNAP25、MYC、NRXN1、GAD2 和 SYT1。 SNAP25 与 M2 巨噬细胞浸润显着相关。数据集 GSE40275 证实了 SNAP25 在 HGNEC 中的高表达和不良预后。 qRT-PCR 和 WB 分析显示 HGNEC 中 SNAP25 和 c-MYC 水平增加，促进 MEK/ERK 通路活性。减少 SNAP25 可降低 H1299 细胞增殖、迁移、侵袭以及 c-MYC、MEK 和 ERK 水平。最后，体内实验进一步证实SNAP25敲除可以抑制肿瘤生长。SNAP25通过刺激MEK/ERK通路调节c-MYC活化，最终影响HGNEC的发育。版权所有©2024 Chen, Wang, Wang, Wang, Qi, An 、孙和林。

This study investigated the expression and role of Synaptosome associated protein 25 (SNAP25) in high-grade neuroendocrine carcinoma (HGNEC).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 in vitro and vivo experiments and datasets.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, in vivo experiments further confirmed that SNAP25 knockout can inhibit tumor growth.SNAP25 regulates c-MYC activation by stimulating the MEK/ERK pathway, ultimately influencing the development of HGNEC.Copyright © 2024 Chen, Wang, Wang, Wang, Qi, An, Sun and Lin.