<p>Di (2-ethylhexyl) phthalate (DEHP) is extremely application in industrial production. DEHP and its metabolites can induce epigenetic changes, such as selective gene expression regulation and post-transcriptional gene regulation, leading to adverse outcome pathways in living organisms. Our findings, bioinformatics tools, and miRNA-mRNA prediction suggested that corticotropin-releasing hormone (<i>CRH</i>) could be miR-101a’s target gene. Although the regulatory relationship between miR-101a and CRH has not been experimentally established, the present study aimed to investigate this interaction in zebrafish embryos exposed to low concentrations of DEHP. Both DLR™ and DFP™ reporter assays confirmed the biological association between miR-101a and <i>CRH</i> mRNA. Validation experiments revealed that overexpression or knockdown of miR-101a in ZF4 cells resulted in changes in <i>CRH</i> mRNA expression. These findings represent that miR-101a adversely impacts CRH at the levels of mRNA.This study improves the discovery of the molecular toxicology of DEHP exposure, and miR-101a is predicted to be a novel toxicological biomarker for chemical hazards.</p>

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The novel regulatory role of miR-101a in CRH expression following low-concentration DEHP exposure in zebrafish embryos

  • Qi Gong,
  • Hossam El Din H. Abdelhafez,
  • Yanqin Ding,
  • Jie Zou,
  • Kai Zhang,
  • Jiangfeng Guo

摘要

Di (2-ethylhexyl) phthalate (DEHP) is extremely application in industrial production. DEHP and its metabolites can induce epigenetic changes, such as selective gene expression regulation and post-transcriptional gene regulation, leading to adverse outcome pathways in living organisms. Our findings, bioinformatics tools, and miRNA-mRNA prediction suggested that corticotropin-releasing hormone (CRH) could be miR-101a’s target gene. Although the regulatory relationship between miR-101a and CRH has not been experimentally established, the present study aimed to investigate this interaction in zebrafish embryos exposed to low concentrations of DEHP. Both DLR™ and DFP™ reporter assays confirmed the biological association between miR-101a and CRH mRNA. Validation experiments revealed that overexpression or knockdown of miR-101a in ZF4 cells resulted in changes in CRH mRNA expression. These findings represent that miR-101a adversely impacts CRH at the levels of mRNA.This study improves the discovery of the molecular toxicology of DEHP exposure, and miR-101a is predicted to be a novel toxicological biomarker for chemical hazards.