研究动态
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微分网络分析揭示了 ECM 受体途径在 α 粒子诱导的恶性转化中的关键作用。

Differential network analysis reveals the key role of the ECM-receptor pathway in α-particle-induced malignant transformation.

发表日期:2024 Sep 10
作者: Wenying Yan, Wentao Hu, Yidan Song, Xingyi Liu, Ziyun Zhou, Wanshi Li, Zhifei Cao, Weiwei Pei, Guangming Zhou, Guang Hu
来源: Molecular Therapy-Nucleic Acids

摘要:

空间粒子辐射是太空飞行中的主要环境因素,已知它会导致身体损伤,甚至引发癌症,但分子病因尚不清楚。为了研究这些原因,我们开发了一种系统生物学方法,重点关注从 BEAS-2B 人类单次高剂量 (SE) 和多次低剂量 (ME) α 粒子辐射暴露获得的转录组学谱的共表达网络分析支气管上皮细胞。首先,基于全局网络和核心模块的差异网络和通路分析表明,ME组中的基因对于细胞外基质(ECM)-受体相互作用通路具有更高的富集度。然后通过网络参数和肺腺癌样本的表达研究,筛选出胶原蛋白基因COL1A1作为ME组的重要基因。通过体外实验分析和体内免疫组织化学染色,发现 COL1A1 促进 BEAS-2B 细胞肿瘤特征的出现。这些结果表明,ME组细胞的恶变程度大于SE组,这可能是由ECM受体通路失调引起的。© 2024 The Author(s).
Space particle radiation is a major environmental factor in spaceflight, and it is known to cause body damage and even trigger cancer, but with unknown molecular etiologies. To examine these causes, we developed a systems biology approach by focusing on the co-expression network analysis of transcriptomics profiles obtained from single high-dose (SE) and multiple low-dose (ME) α-particle radiation exposures of BEAS-2B human bronchial epithelial cells. First, the differential network and pathway analysis based on the global network and the core modules showed that genes in the ME group had higher enrichment for the extracellular matrix (ECM)-receptor interaction pathway. Then, collagen gene COL1A1 was screened as an important gene in the ME group assessed by network parameters and an expression study of lung adenocarcinoma samples. COL1A1 was found to promote the emergence of the neoplastic characteristics of BEAS-2B cells by both in vitro experimental analyses and in vivo immunohistochemical staining. These findings suggested that the degree of malignant transformation of cells in the ME group was greater than that of the SE, which may be caused by the dysregulation of the ECM-receptor pathway.© 2024 The Author(s).