Yang Dacheng, Li Qian, Chen Zisheng, Zhang Wei Kevin
School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.
Guangzhou National Laboratory, Guangzhou, Guangdong, China.
Front Oncol. 2025 Aug 22;15:1645671. doi: 10.3389/fonc.2025.1645671. eCollection 2025.
Endothelial cells play a critical role in tumor-associated vasculature formation and immune modulation, and dysregulation of transcription factors (TFs) such as Meox1 has been associated with various cancers, including non-small cell lung cancer (NSCLC). Meox1 has been implicated in promoting both tumor-promoting and immune-suppressing functions.
In this study, to systematically map TF dynamics across cancer and immune cells, we performed scRNA-seq on tumor tissues and used the SCENIC framework for regulon analysis, revealing cell-type-specific gene regulatory networks. We investigated the functional role of Meox1 in NSCLC by employing a siRNA-based knockdown approach to selectively reduce its expression.
Our preliminary findings reveal that siRNA-mediated Meox1 knockdown significantly impairs the capacity of tube formation at the cellular level. Furthermore, we observed a marked reduction in tumor cell proliferation and an increase in CD8 expression, a marker of T-cell activity in an animal model system, indicating that Meox1 may also play a regulatory role in immune-mediated tumor suppression.
Our findings not only deepen our understanding of the molecular mechanisms underlying lung cancer progression but also open new avenues for the development of targeted therapies aimed at restoring tumor-associated endothelial cell function and enhancing immune responses against cancer.
内皮细胞在肿瘤相关血管形成和免疫调节中起关键作用，转录因子（TFs）如Meox1的失调与包括非小细胞肺癌（NSCLC）在内的多种癌症相关。Meox1被认为在促进肿瘤促进和免疫抑制功能方面都发挥作用。
在本研究中，为了系统地描绘癌症和免疫细胞中的转录因子动态，我们对肿瘤组织进行了单细胞RNA测序（scRNA-seq），并使用SCENIC框架进行调控子分析，揭示细胞类型特异性基因调控网络。我们通过采用基于小干扰RNA（siRNA）的敲低方法选择性降低其表达，研究了Meox1在NSCLC中的功能作用。
我们的初步研究结果表明，siRNA介导的Meox1敲低在细胞水平上显著损害了管形成能力。此外，我们在动物模型系统中观察到肿瘤细胞增殖明显减少，以及T细胞活性标志物CD8表达增加，这表明Meox1在免疫介导的肿瘤抑制中也可能发挥调节作用。
我们的研究结果不仅加深了我们对肺癌进展潜在分子机制的理解，还为开发旨在恢复肿瘤相关内皮细胞功能和增强抗癌免疫反应的靶向治疗开辟了新途径。
