BPA暴露对本体和子代胰岛β细胞转录组差异对比分析
Analysis of the differences of BPA exposure on the transcriptome of islet cells between adults and offspring
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摘要: 双酚A (BPA)作为一种典型的环境内分泌干扰物,与二型糖尿病和肥胖症等代谢类疾病密切相关.在这项研究中,旨在探讨BPA直接暴露以及围产期暴露对本体和子代胰岛β细胞影响的差异,从而实现对不同易感人群的精准预防与治疗.通过对GEO数据库中GSE126297和GSE82175两个数据集进行分析,共筛选出108个共有的差异基因,其中28个表达趋势一致,而另外80个表达趋势相反.随后对本体和子代单独的差异基因,以及共有差异基因进行了GO和KEGG对比分析.此外,利用String数据库和Cytoscape分析PPI网络中的紧密联系的基因,并将其可视化,进一步从28个表达趋势一致的基因中筛选出相互作用最为紧密的基因集1(Iqgap2,Igf2r和Rab18);从80个表达趋势相反的基因中筛选出相互作用紧密的基因集2(Polr2f,Ccnt2,Polr2e,Kdm7a,Fbl)和基因集3(Atp5g2,Atp5o和Ndufa6).最后,通过GEPIA在线验证上述基因在胰腺癌样本中的表达,研究发现Rab18,Polr2f,Polr2e,Fbl,Atp5g2,Atp5o和Ndufa6在胰腺癌病例中的表达均显著上升.同时,上述基因在本体中呈现显著上升趋势,而对于子代,只有Rab18显著上升,其他基因则呈下降趋势.综上,BPA对本体和子代的影响有一定的关联,其中关联的关键基因的异常表达可能会增加本体罹患胰腺癌的风险,而对于子代则会影响代谢过程和细胞结构.Abstract: Bisphenol-A (BPA) is a represent endocrine-disrupting chemical that has been proposed to be associated with type 2 diabetes and obesity. The present study aimed to investigate the differences between BPA direct exposure and maternal exposure on the transcriptome of islet cells in adults and offspring, and then to achieve accurate prevention and treatment of different sensitive population. By analyzing the two data sets of GSE126297 and GSE82175 collected from the GEO database, a total of 108 shared differentially expressed gene (DEG) between the two data sets were screened out, of which 28 showed the similar expression trend, while the other 80 showed the opposite expression trend. Subsequently, the GO and KEGG comparative analysis were carried out with the DEGs only in adult and offspring, and those DEGs in both groups. Then, PPI network and visualization was conducted using String database and Cytoscape software. the most closely interacting genes of gene set 1 (Iqgap2, Igf2r and Rab18) were screened from the 28 genes with the same expression trend, similarly genes of gene set 2 (Polr2f, Ccnt2, Polr2e, Kdm7a, Fbl) and those of gene set 3 (Atp5g2, Atp5o and Ndufa6) were screened from the 80 genes with opposite trend. Finally, GEPIA was used to verify the expression levels of these genes in pancreatic cancer samples, the results showed that Rab18, Polr2f, Polr2e, Fbl, Atp5g2, Atp5o and Ndufa6 was increased significantly in pancreatic cancer. In addition, these genes also showed a significant increase in adult; as for the offspring, only Rab18 increased significantly, while other genes showed a downward trend. Taken together, the influence of BPA on adult is related to that on the offspring. The abnormally expressed key genes may increase the risk of pancreatic cancer of adult, and affect the metabolic process and cell structure of the offspring.
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Key words:
- bisphenol-A (BPA) /
- adult and offspring /
- islet β cells /
- bioinformatic analysis
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