Genome-wide identification of the interactions between key genes and pathways provide new insights into the toxicity of bisphenol F and S during early development in zebrafish
Genome-wide identification of the interactions between key genes and pathways provide new insights into the toxicity of bisphenol F and S during early development in zebrafish
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对关键基因和通路之间相互作用的全基因组鉴定为斑马鱼早期发育过程中双酚 F 和 S 的毒性提供了新的见解
DOI：
10.1016/j.chemosphere.2018.09.133
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发表时间：
2018
期刊：
影响因子：
8.8
通讯作者：
Zheng Chunmiao
中科院分区：
文献类型：
--
作者：
Yang Feng;Qiu Wenhui;Li Rongzhen;Hu Jiaqi;Luo Shusheng;Zhang Ting;He Xin;Zheng Chunmiao
双酚F（BPF）和双酚S（BPS）已被广泛用作双酚A（BPA）的替代品。随着其使用量的增加，BPF和BPS也被释放到环境中;因此，其对水生生物和人类的潜在风险正引起人们的关注。本研究的目的是确定关键途径和枢纽基因之间的相互作用，在斑马鱼的BPF和BPS暴露后，并评估对人类健康的潜在风险。我们通过KEGG过度表达检验和基因集富集分析（GSEA）确定了三个关键通路：“坏死性凋亡”、“脂肪细胞因子信号通路”和“C型凝集素受体信号通路”。此外，三个枢纽基因（mstlra，prkcdb，和pik 3cb）和详细的相互作用的途径进行了研究，通过分析PPI网络，亚细胞定位，和最短的途径。令人惊讶的是，所有这三种途径都与癌症的潜在风险密切相关，正如之前报道的那样。此外，在使用人类BPF或BPS相关基因的途径富集分析中，KOBAS在“癌症途径”和“癌症”中显示的结果属于前10个术语，如使用GenCLiP发现的。此外，使用人类中枢基因的同源基因（MST 1 R、PIK 3CB和PRKCD）进行Kaplan-Meier生存分析，以评估双酚暴露是否会对乳腺癌产生不利影响。总之，这些研究证明了BPF和BPS的潜在致癌性。据我们所知，这是第一次研究三个重叠的关键途径和三个枢纽基因，以探讨BPF和BPS的相关机制和随后的相互作用在斑马鱼。
Bisphenol F (BPF) and bisphenol S (BPS) have been widely used as alternatives to bisphenol A (BPA). With their increasing use, BPF and BPS have also been released into the environment; thus, their potential risks to aquatic organisms and humans are drawing attention. The objective of this study was to identify the interactions between key pathways and hub genes in zebrafish following BPF and BPS exposure, and to evaluate the potential risks to human health. We identified three key pathways using KEGG over-representation test and Gene Set Enrichment Analysis (GSEA): 'Necroptosis,'Adipocytokine signaling pathway,' and 'C-type lectin receptor signaling pathway.' Moreover, three hub genes (mstlra, prkcdb, and pik3cb) and detailed interactions among the pathways were examined by the analyses of PPI network, subcellular location, and shortest-pathway. Surprisingly, all three pathways were strongly associated with a potential risk of cancer, as reported previously. In addition, the results of KOBAS shown in 'Pathways in Cancer' and 'Cancers' belong to the top 10 terms in pathway enrichment analyses using genes related to BPF or BPS in human, as was found using GenCLiP. Moreover, the Kaplan-Meier survival analysis was performed using homologenes (MST1R, PIK3CB and PRKCD) of hub genes in human to evaluate whether exposure to bisphenols may adversely affect breast cancer. Taken together, these studies demonstrate the potential carcinogenicity of BPF and BPS. To our knowledge, this is the first study on three overlapping key pathways and three hub genes to investigate BPF and BPS exposure-related mechanisms and subsequent interactions in zebrafish.