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双酚A诱导的DNA损伤通过异常的CTNNB1信号通路促进人淋巴母细胞淋巴瘤的进展。

Bisphenol A-induced DNA damages promote to lymphoma progression in human lymphoblastoid cells through aberrant CTNNB1 signaling pathway.

作者信息

Chen Yin-Kai, Tan Yan-Yan, Yao Min, Lin Ho-Chen, Tsai Mon-Hsun, Li Yu-Yun, Hsu Yih-Jen, Huang Tsung-Tao, Chang Chia-Wei, Cheng Chih-Ming, Chuang Chun-Yu

机构信息

Department of Hematology, National Taiwan University Cancer Center, Taipei, 106, Taiwan.

Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101, section 2, Kuang-Fu Road, Hsinchu, 30013, Taiwan.

出版信息

iScience. 2021 Jul 21;24(8):102888. doi: 10.1016/j.isci.2021.102888. eCollection 2021 Aug 20.

Abstract

Lymphoma is a group of blood cancers that develop from the immune system, and one of the main risk factors is associated with exposure to environmental chemicals. Bisphenol A (BPA) is a common chemical used in the manufacture of materials in polycarbonate and epoxy plastic products and can interfere with the immune system. BPA is considered to possibly induce lymphoma development by affecting the immune system, but its potential mechanisms have not been well established. This study performed a gene-network analysis of microarray data sets in human lymphoma tissues as well as in human cells with BPA exposure to explore module genes and construct the potential pathway for lymphomagenesis in response to BPA. This study provided evidence that BPA exposure resulted in disrupted cell cycle and DNA damage by activating CTNNB1, the initiator of the aberrant constructed CTNNB1-NFKB1-AR-IGF1-TWIST1 pathway, which may potentially lead to lymphomagenesis.

摘要

淋巴瘤是一组起源于免疫系统的血液癌症,主要风险因素之一与接触环境化学物质有关。双酚A(BPA)是一种常用于制造聚碳酸酯和环氧塑料制品材料的常见化学物质,可干扰免疫系统。双酚A被认为可能通过影响免疫系统诱导淋巴瘤的发生,但其潜在机制尚未完全明确。本研究对人类淋巴瘤组织以及暴露于双酚A的人类细胞中的微阵列数据集进行了基因网络分析,以探索模块基因并构建双酚A诱导淋巴瘤发生的潜在途径。本研究提供的证据表明,暴露于双酚A会通过激活CTNNB1导致细胞周期紊乱和DNA损伤,CTNNB1是异常构建的CTNNB1-NFKB1-AR-IGF1-TWIST1途径的启动子,这可能潜在地导致淋巴瘤的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bc6/8350018/e37884fe122e/fx1.jpg

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