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

差异网络分析揭示 ECM 受体通路在 α 粒子诱发恶性转化中的关键作用

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作者:Wenying Yan, Wentao Hu, Yidan Song, Xingyi Liu, Ziyun Zhou, Wanshi Li, Zhifei Cao, Weiwei Pei, Guangming Zhou, Guang Hu

Abstract

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.

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