文章：

通过多组学解析毛蕊异黄酮在肺腺癌中的抗癌机制：靶向肿瘤微环境中SMAD3介导的NOTCH信号通路

Deciphering Anticancer Mechanisms of Calycosin in Lung Adenocarcinoma Through Multi-Omics: Targeting SMAD3-Mediated NOTCH Signaling in the Tumor Microenvironment

原文发布日期：26 April 2025

DOI: 10.3390/cancers17091455

类型: Article

开放获取: 是

英文摘要：

Objective: Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, particularly in advanced stages. This study investigates the anticancer mechanisms of calycosin, an isoflavonoid derived fromAstragalus membranaceus, in LUAD. Methods: Using integrative approaches including bulk and single-cell RNA sequencing, network pharmacology, and molecular docking, we identified SMAD3 as a critical biomarker associated with LUAD staging and prognosis. Results: Calycosin targets SMAD3, modulating the NOTCH signaling pathway in monocytes/macrophages to suppress tumor growth, invasion, and immune evasion. Enrichment analyses revealed significant involvement of NOTCH signaling components in SMAD3-correlated genes, particularly in advanced-stage LUAD. Single-cell RNA sequencing further demonstrated NOTCH pathway enrichment in tumor-associated monocytes/macrophages. Additionally, KMT2A was identified as a key transcriptional regulator in these cells. Conclusions: These findings highlight the potential effects of calycosin and provide novel insights into targeting the tumor–immune microenvironment in LUAD.

摘要翻译： 

目的：肺腺癌（LUAD）仍是癌症相关死亡的主要原因，尤其在晚期阶段。本研究探讨源自黄芪的异黄酮类化合物毛蕊异黄酮在肺腺癌中的抗癌机制。方法：通过整合性方法，包括批量与单细胞RNA测序、网络药理学及分子对接技术，我们鉴定出SMAD3作为与肺腺癌分期及预后相关的关键生物标志物。结果：毛蕊异黄酮靶向SMAD3，通过调节单核细胞/巨噬细胞中的NOTCH信号通路，抑制肿瘤生长、侵袭及免疫逃逸。富集分析显示NOTCH信号通路成分在SMAD3相关基因中显著富集，尤其在晚期肺腺癌中。单细胞RNA测序进一步证实肿瘤相关单核细胞/巨噬细胞中NOTCH通路富集。此外，KMT2A被鉴定为这些细胞中的关键转录调控因子。结论：这些发现揭示了毛蕊异黄酮的潜在作用机制，并为靶向肺腺癌肿瘤-免疫微环境提供了新的见解。

原文链接：

Deciphering Anticancer Mechanisms of Calycosin in Lung Adenocarcinoma Through Multi-Omics: Targeting SMAD3-Mediated NOTCH Signaling in the Tumor Microenvironment