SNAP25诱导的MYC上调促进了高级神经内分泌肺癌的进展
SNAP25-induced MYC upregulation promotes high-grade neuroendocrine lung carcinoma progression
影响因子:5.90000
分区:医学2区 / 免疫学2区
发表日期:2024
作者:
Zhiqiang Chen, Shujing Wang, Jingrui Wang, Ying Wang, Xiangjun Qi, Bo An, Lingling Sun, Lizhu Lin
摘要
这项研究研究了突触体相关蛋白25（SNAP25）在高级神经内分泌癌（HGNEC）中的表达和作用。我们使用差异表达的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曲线评估了它们的诊断价值。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发现。WGCNA鉴定了与MAPK信号，GABA能突触以及癌症相关的转录错误相关的595个关键基因。顶级基因包括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中的高表达和预后不良。 QRT-PCR和WB分析显示，HGNEC中的SNAP25和C-MYC水平升高，促进MEK/ERK途径活动。减少SNAP25降低了H1299的细胞增殖，迁移，侵袭和C-Myc，MEK和ERK的水平。最后，体内实验进一步证实了SNAP25敲除可以抑制肿瘤的生长。SNAP25通过刺激MEK/ERK途径来调节C-MYC激活，最终影响HGNEC的发展。
Abstract
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.