Cited by 16Effects and risks of endocrine disrupting chemicalsMicroRNA in disease regulationNeurogenesis and neuroplasticity mechanisms

MiR-93 alleviates DEHP plasticizer-induced neurotoxicity by negatively regulating TNFAIP1 and inhibiting ubiquitin-mediated degradation of CK2β

Qiu, Feng, He, Simei, Zhang, Zilong, Dai, Siyu, Wang, Jin, Liu, Ning, Li, Zhiwei, Hu, Xiang +2 more·2023·Food and Chemical Toxicology

Abstract

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is widely used in various products, such as plastic packaging in food industries. As an environmental endocrine disruptor, it induces adverse effects on brain development and function. However, the molecular mechanisms by which DEHP induces learning and memory impairment remain poorly understood. Herein, we found that DEHP impaired learning and memory in pubertal C57BL/6 mice, decreased the number of neurons, downregulated miR-93 and the β subunit of casein kinase 2 (CK2β), upregulated tumor necrosis factor-induced protein 1 (TNFAIP1), and inhibited Akt/CREB pathway in mouse hippocampi. Co-immunoprecipitation and western blotting assays revealed that TNFAIP1 interacted with CK2β and promoted its degradation by ubiquitination. Bioinformatics analysis showed a miR-93 binding site in the 3'-untranslated region of Tnfaip1. A dual-luciferase reporter assay revealed that miR-93 targeted TNFAIP1 and negatively regulated its expression. MiR-93 overexpression prevented DEHP-induced neurotoxicity by downregulating TNFAIP1 and then activating CK2/Akt/CREB pathway. These data indicate that DEHP upregulates TNFAIP1 expression by downregulating miR-93, thus promoting ubiquitin-mediated degradation of CK2β, subsequently inhibiting Akt/CREB pathway, and finally inducing learning and memory impairment. Therefore, miR-93 can relieve DEHP-induced neurotoxicity and may be used as a potential molecular target for prevention and treatment of…

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Crossref · 10.1016/j.fct.2023.113888

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Authors
Qiu, F., He, S., Zhang, Z., Dai, S., Wang, J., Liu, N., Li, Z., Hu, X., Xiang, S., & Wei, C.
Affiliations
Hunan Normal University (CN)
Corresponding author
Wei, Chenxi
Venue
Food and Chemical Toxicology
Publisher
Elsevier BV
Published
2023-08
Volume
178
Pages
113888
ISSN
0278-6915 (ISSN-L)
OpenAlex
W4380153988
Cited by
16
References
86
Citations by year
2026: 4 · 2025: 9 · 2024: 1 · 2023: 2
FWCI
1.83
Type
journal article
Language
en
Open access
closed
Locations
  • Food and Chemical Toxicology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Natural Science Foundation of Hunan Province (2018JJ3330)
  • National Natural Science Foundation of China (21806036, 81972642)
  • Hunan Normal University
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
miR-93, DEHP, TNFAIP1, CK2β, ubiquitin-mediated proteolysis, learning and memory impairment, hippocampus, endocrine disruptors, microRNA target regulation, 3' untranslated region
MeSH terms
Animals, Carrier Proteins, Diethylhexyl Phthalate, Mice, Inbred C57BL, Plasticizers, Transcription Factors, Ubiquitin, MicroRNAs, Adaptor Proteins, Signal Transducing, Proto-Oncogene Proteins c-akt, Mice

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