Autor: |
Lujia Zhang, Liuqing Yang, Jianwei Gao, Li Dong, Yinghua Luo, Fang Chen |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
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Zdroj: |
Food Frontiers, Vol 5, Iss 2, Pp 607-617 (2024) |
Druh dokumentu: |
article |
ISSN: |
2643-8429 |
DOI: |
10.1002/fft2.336 |
Popis: |
Abstract Acrylamide (AA) is a neurotoxic and potentially carcinogenic contaminant, usually generated during food processing. MicroRNAs are a class of noncoding small RNAs, which serve essential pathogenic roles in linking exposure to toxic contaminants with their pathological outcomes. Our previous research identified miR‐27a‐5p as a key regulator in AA toxicity, as it induces mitochondria‐dependent apoptosis by targeting Btf3 in rats. However, the mechanisms by which miR‐27a‐5p is regulated to exert its toxic effects remain unclear. Here, the transcription factors that bind to the promoter of miR‐27a‐5p and their potential regulatory functions are investigated in cell lines and rats. The results showed that nuclear factor kappa‐B 1 (NF‐κB1) is a promising transcription factor from bioinformatic analysis. The luciferase reporter assay demonstrated that NF‐κB1 enhances the transcriptional activity of the miR‐27a‐5p promoter, whereas the cleavage under targets and tagmentation assay successfully verified the specific binding sites at −305/−298 bp. Furthermore, the inhibition of NF‐κB1 resulted in the suppression of miR‐27a‐5p expression and its associated target pathways, with additional validation provided by in vivo experimentation. Consequently, the upregulation of miR‐27a‐5p induced by AA and its subsequent intrinsic apoptosis can be attributed to the binding of NF‐κB1 to the miR‐27a‐5p promoter. This binding event may serve as the initial step in the molecular network regulated by miR‐27a‐5p that underlies AA toxicity. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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