School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China.
State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, Fujian, 361005, China.
Fish Shellfish Immunol. 2020 May;100:152-160. doi: 10.1016/j.fsi.2020.03.006. Epub 2020 Mar 5.
Bisphenol A (BPA), a well-known environmental endocrine-disrupting chemical (EDC), could pose a great toxicity risk to aquatic organisms. The present study aimed to evaluate the underlying role of long non-coding RNAs (lncRNAs) in BPA-induced immunotoxicity in head kidney (HK) macrophages of the red common carp (Cyprinus carpio), using lncRNA-RNA sequencing (RNA-Seq). In BPA-exposed HK macrophages group, 2,095 and 1,138 differentially expressed mRNAs (DEGs) and lncRNAs (DE-lncRNAs) were obtained, respectively, compared with controls. The qRT-PCR validation results of DEGs and DE-lncRNAs were similar to the RNA-Seq results. The KEGG analysis of DEGs and target genes of DE-lncRNAs have shown that some immune-related signaling pathways, including NF-kappa B, Toll-like receptor, B-cell receptor, Jak-STAT, and Hippo signaling pathways, were severely disrupted by BPA exposure. Moreover, we observed the synergic regulation of some mRNAs involved in immune response such as two hub genes traf6 and mapk1/3 and their upstream lncRNAs in HK macrophages upon the BPA exposure or its analogue bisphenol S (BPS) exposure. This suggested the dysregulation of lncRNAs by BPA or BPS may lead to a change in the expression of hub genes, which affects the cross-talk of various signaling pathways by interaction with other network genes. In conclusion, the present study demonstrates the potential role of lncRNAs in immunotoxicity of bisphenol compounds in red common carp HK macrophages, and our results provide evidence for further exploring lncRNA's role in EDC-induced toxicity in aquatic organisms.
双酚 A（BPA）是一种众所周知的环境内分泌干扰化学物质（EDC），可能对水生生物造成极大的毒性风险。本研究旨在使用长非编码 RNA（lncRNA）测序（RNA-Seq）评估 lncRNA 在 BPA 诱导的红鲤（Cyprinus carpio）头肾（HK）巨噬细胞免疫毒性中的潜在作用。与对照组相比，BPA 暴露的 HK 巨噬细胞组分别获得了 2095 个和 1138 个差异表达的 mRNA（DEGs）和 lncRNA（DE-lncRNAs）。DEGs 和 DE-lncRNAs 的 qRT-PCR 验证结果与 RNA-Seq 结果相似。DEGs 和 DE-lncRNAs 靶基因的 KEGG 分析表明，一些免疫相关信号通路，包括 NF-kappa B、Toll 样受体、B 细胞受体、Jak-STAT 和 Hippo 信号通路，受到 BPA 暴露的严重破坏。此外，我们观察到在 BPA 或其类似物双酚 S（BPS）暴露下，一些参与免疫反应的 mRNAs（如两个枢纽基因 traf6 和 mapk1/3 及其上游 lncRNAs）在 HK 巨噬细胞中的协同调节作用。这表明 BPA 或 BPS 对 lncRNA 的失调可能导致枢纽基因表达的改变，从而通过与其他网络基因的相互作用影响各种信号通路的串扰。总之，本研究表明 lncRNA 在红鲤 HK 巨噬细胞中双酚化合物免疫毒性中的潜在作用，我们的结果为进一步探索 lncRNA 在水生生物中 EDC 诱导毒性中的作用提供了证据。
