PMID- 35835386 OWN - NLM STAT- MEDLINE DCOM- 20220817 LR - 20220817 IS - 1095-9947 (Electronic) IS - 1050-4648 (Linking) VI - 127 DP - 2022 Aug TI - Toxicological effects of polystyrene nanoplastics and perfluorooctanoic acid to Gambusia affinis. PG - 1100-1112 LID - S1050-4648(22)00382-5 [pii] LID - 10.1016/j.fsi.2022.06.064 [doi] AB - Plastic pollution has attracted huge attention from public and scientific community in recent years. In the environment, nanoplastics (NPs, <100 nm) can interact with persistent organic pollutants (POPs) such as perfluorooctanoic acid (PFOA) and may exacerbate associated toxic impacts. The present study aims to explore the single and combined ecotoxicological effects of PFOA and polystyrene nanoplastics (PS-NPs, 80 nm) on the PI3K/AKT3 signaling pathway using a freshwater fish model Gambusia affinis. Fish were exposed individually to PS-NPs (200 mug/L) and PFOA (50, 500, 5000 mug/L) and their chemical mixtures for 96 h. Our results showed that the co-exposure significantly altered the mRNA relative expression of PI3K, AKT3, IKKbeta and IL-1beta, compared to corresponding single exposure and control groups, indicating that the PFOA-NP co-exposure can activate the PI3K/AKT3 signaling pathway. The bioinformatic analyses showed that AKT3 had more probes and exhibited a significantly sensitive correlation with DNA methylation, compared to other genes (PIK3CA, IKBKB, and IL1B). Further, the mRNA expressions of PIK3CA, AKT3, and IKBKB had a significant correlation with copy number variation (CNV) in human liver hepatocellular carcinoma (LIHC). And PIK3CA had the highest mutation rate among other genes of interest for LIHC. Moreover, AKT3 showed a relatively lower expression in TAM and CAF cells, compared to PIK3CA, IKBKB, and IL1B. Besides, hsa-mir-155-5p was closely correlated with AKT3, PIK3CA, IKBKB, and IL1B. In summary, these results provide evidence that NPs could enhance the carcinogenic effects of POPs on aquatic organisms and highlight possible targets of LIHC induced by PFOA-NP co-exposure. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Liu, Shulin AU - Liu S AD - College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China. FAU - Yan, Lei AU - Yan L AD - College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China. FAU - Zhang, Yanling AU - Zhang Y AD - College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China. FAU - Junaid, Muhammad AU - Junaid M AD - College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China. FAU - Wang, Jun AU - Wang J AD - College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China; Institute of Eco-Environmental Research, Guangxi Academy of Sciences, Nanning, 530007, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, 528478, China. Electronic address: wangjun2016@scau.edu.cn. LA - eng PT - Journal Article DEP - 20220711 PL - England TA - Fish Shellfish Immunol JT - Fish & shellfish immunology JID - 9505220 RN - 0 (Caprylates) RN - 0 (Fluorocarbons) RN - 0 (Microplastics) RN - 0 (Polystyrenes) RN - 0 (RNA, Messenger) RN - 0 (Water Pollutants, Chemical) RN - 947VD76D3L (perfluorooctanoic acid) RN - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.10 (I-kappa B Kinase) SB - IM MH - Animals MH - Caprylates MH - Class I Phosphatidylinositol 3-Kinases MH - *Cyprinodontiformes/genetics/metabolism MH - DNA Copy Number Variations MH - Fluorocarbons MH - Humans MH - I-kappa B Kinase MH - Microplastics/toxicity MH - *Nanoparticles/chemistry MH - Phosphatidylinositol 3-Kinases MH - Polystyrenes/toxicity MH - RNA, Messenger MH - *Water Pollutants, Chemical/metabolism OTO - NOTNLM OT - Liver hepatocellular carcinoma OT - Nanoplastics OT - PI3K/AKT3 signaling pathway OT - Perfluorooctanoic acid OT - TCGA EDAT- 2022/07/15 06:00 MHDA- 2022/08/18 06:00 CRDT- 2022/07/14 19:37 PHST- 2022/05/18 00:00 [received] PHST- 2022/06/22 00:00 [revised] PHST- 2022/06/27 00:00 [accepted] PHST- 2022/07/15 06:00 [pubmed] PHST- 2022/08/18 06:00 [medline] PHST- 2022/07/14 19:37 [entrez] AID - S1050-4648(22)00382-5 [pii] AID - 10.1016/j.fsi.2022.06.064 [doi] PST - ppublish SO - Fish Shellfish Immunol. 2022 Aug;127:1100-1112. doi: 10.1016/j.fsi.2022.06.064. Epub 2022 Jul 11.