Whole-transcriptome analysis of aluminum-exposed rat hippocampus and identification of ceRNA networks to investigate neurotoxicity of Al
Aluminum is a known neurotoxin that can induce Aβ deposition and abnormal phosphorylation of tau protein, leading to Alzheimer disease (AD)-like damages such as neuronal damage and decreased learning and memory functions. In this study, we constructed a rat model of subchronic aluminum maltol exposu...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253121002857 |
| _version_ | 1818723537723064320 |
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| author | Chanting He Xiaoyan Zhao Yang Lei Jisheng Nie Xiaoting Lu Jing Song Linping Wang Huan Li Fangqu Liu Yidan Zhang Qiao Niu |
| author_facet | Chanting He Xiaoyan Zhao Yang Lei Jisheng Nie Xiaoting Lu Jing Song Linping Wang Huan Li Fangqu Liu Yidan Zhang Qiao Niu |
| author_sort | Chanting He |
| collection | DOAJ |
| description | Aluminum is a known neurotoxin that can induce Aβ deposition and abnormal phosphorylation of tau protein, leading to Alzheimer disease (AD)-like damages such as neuronal damage and decreased learning and memory functions. In this study, we constructed a rat model of subchronic aluminum maltol exposure, and the whole-transcriptome sequencing was performed on the hippocampus of the control group and the middle-dose group. A total of 167 miRNAs, 37 lncRNAs, 256 mRNAs, and 64 circRNAs expression changed. The Kyoto Encyclopedia of Genes and Genomes showed that PI3K/AKT pathway was the most enriched pathway of DEGs, and IRS1 was the core molecule in the PPI network. circRNA/lncRNA-miRNA-mRNA networks of all DEGs, DEGs in the PI3K/AKT pathway, and IRS1 were constructed by Cytoscape. Molecular experiment results showed that aluminum inhibited the IRS1/PI3K/AKT pathway and increased the content of Aβ and tau. In addition, we also constructed an AAV intervention rat model, proving that inhibition of miR-96-5p expression might resist aluminum-induced injury by upregulating expression of IRS1. In general, these results suggest that the ceRNA networks are involved in the neurotoxic process of aluminum, providing a new strategy for studying the toxicity mechanism of aluminum and finding biological targets for the prevention and treatment of AD. |
| first_indexed | 2024-12-17T21:12:06Z |
| format | Article |
| id | doaj.art-60f202ae9a7441daa5f4c4f69498f8c6 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-17T21:12:06Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-60f202ae9a7441daa5f4c4f69498f8c62022-12-21T21:32:26ZengElsevierMolecular Therapy: Nucleic Acids2162-25312021-12-012614011417Whole-transcriptome analysis of aluminum-exposed rat hippocampus and identification of ceRNA networks to investigate neurotoxicity of AlChanting He0Xiaoyan Zhao1Yang Lei2Jisheng Nie3Xiaoting Lu4Jing Song5Linping Wang6Huan Li7Fangqu Liu8Yidan Zhang9Qiao Niu10Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Lab of Cellular Physiology of Education Ministry, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Department of Anatomy, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaDepartment of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaDepartment of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaDepartment of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaDepartment of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaDepartment of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaDepartment of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaDepartment of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaDepartment of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaDepartment of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaDepartment of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Lab of Cellular Physiology of Education Ministry, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Corresponding author: Qiao Niu, PhD, Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China.Aluminum is a known neurotoxin that can induce Aβ deposition and abnormal phosphorylation of tau protein, leading to Alzheimer disease (AD)-like damages such as neuronal damage and decreased learning and memory functions. In this study, we constructed a rat model of subchronic aluminum maltol exposure, and the whole-transcriptome sequencing was performed on the hippocampus of the control group and the middle-dose group. A total of 167 miRNAs, 37 lncRNAs, 256 mRNAs, and 64 circRNAs expression changed. The Kyoto Encyclopedia of Genes and Genomes showed that PI3K/AKT pathway was the most enriched pathway of DEGs, and IRS1 was the core molecule in the PPI network. circRNA/lncRNA-miRNA-mRNA networks of all DEGs, DEGs in the PI3K/AKT pathway, and IRS1 were constructed by Cytoscape. Molecular experiment results showed that aluminum inhibited the IRS1/PI3K/AKT pathway and increased the content of Aβ and tau. In addition, we also constructed an AAV intervention rat model, proving that inhibition of miR-96-5p expression might resist aluminum-induced injury by upregulating expression of IRS1. In general, these results suggest that the ceRNA networks are involved in the neurotoxic process of aluminum, providing a new strategy for studying the toxicity mechanism of aluminum and finding biological targets for the prevention and treatment of AD.http://www.sciencedirect.com/science/article/pii/S2162253121002857aluminumRNA sequencingceRNAPI3K/AKT pathwayIRS1miR-96-5p |
| spellingShingle | Chanting He Xiaoyan Zhao Yang Lei Jisheng Nie Xiaoting Lu Jing Song Linping Wang Huan Li Fangqu Liu Yidan Zhang Qiao Niu Whole-transcriptome analysis of aluminum-exposed rat hippocampus and identification of ceRNA networks to investigate neurotoxicity of Al Molecular Therapy: Nucleic Acids aluminum RNA sequencing ceRNA PI3K/AKT pathway IRS1 miR-96-5p |
| title | Whole-transcriptome analysis of aluminum-exposed rat hippocampus and identification of ceRNA networks to investigate neurotoxicity of Al |
| title_full | Whole-transcriptome analysis of aluminum-exposed rat hippocampus and identification of ceRNA networks to investigate neurotoxicity of Al |
| title_fullStr | Whole-transcriptome analysis of aluminum-exposed rat hippocampus and identification of ceRNA networks to investigate neurotoxicity of Al |
| title_full_unstemmed | Whole-transcriptome analysis of aluminum-exposed rat hippocampus and identification of ceRNA networks to investigate neurotoxicity of Al |
| title_short | Whole-transcriptome analysis of aluminum-exposed rat hippocampus and identification of ceRNA networks to investigate neurotoxicity of Al |
| title_sort | whole transcriptome analysis of aluminum exposed rat hippocampus and identification of cerna networks to investigate neurotoxicity of al |
| topic | aluminum RNA sequencing ceRNA PI3K/AKT pathway IRS1 miR-96-5p |
| url | http://www.sciencedirect.com/science/article/pii/S2162253121002857 |
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