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c-Jun targets miR-451a to regulate HQ-induced inhibition of erythroid differentiation via the BATF/SETD5/ARHGEF3 axis.
- Source :
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Toxicology . Jun2024, Vol. 505, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
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Abstract
- Benzene, a widely used industrial chemical, has been clarified to cause hematotoxicity. Our previous study suggested that miR-451a may play a role in benzene-induced impairment of erythroid differentiation. However, the mechanism underlying remains unclear. In this study, we explored the role of miR-451a and its underlying mechanisms in hydroquinone (HQ)-induced suppression of erythroid differentiation in K562 cells. 0, 1.0, 2.5, 5.0, 10.0, and 50 μM HQ treatment of K562 cells resulted in a dose-dependent inhibition of erythroid differentiation, as well as the expression of miR-451a. Bioinformatics analysis was conducted to predict potential target genes of miR-451a and dual-luciferase reporter assays confirmed that miR-451a can directly bind to the 3'-UTR regions of BATF, SETD5, and ARHGEF3 mRNAs. We further demonstrated that over-expression or down-regulation of miR-451a altered the expression of BATF, SETD5, and ARHGEF3, and also modified erythroid differentiation. In addition, BATF, SETD5, and ARHGEF3 were verified to play a role in HQ-induced inhibition of erythroid differentiation in this study. Knockdown of SETD5 and ARHGEF3 reversed HQ-induced suppression of erythroid differentiation while knockdown of BATF had the opposite effect. On the other hand, we also identified c-Jun as a potential transcriptional regulator of miR-451a. Forced expression of c-Jun increased miR-451a expression and reversed the inhibition of erythroid differentiation induced by HQ, whereas knockdown of c-Jun had the opposite effect. And the binding site of c-Jun and miR-451a was verified by dual-luciferase reporter assay. Collectively, our findings indicate that miR-451a and its downstream targets BATF, SETD5, and ARHGEF3 are involved in HQ-induced erythroid differentiation disorder, and c-Jun regulates miR-451a as a transcriptional regulator in this process. [Display omitted] • HQ inhibited erythroid differentiation and miR-451a expression in K562 cells. • miR-451a modulates erythroid differentiation by targeting BATF, SETD5, ARHGEF3. • c-Jun regulates miR-451a to participate in HQ-induced erythroid differentiation disorder. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HYDROQUINONE
*BINDING sites
*CELL differentiation
*ERYTHROCYTE membranes
Subjects
Details
- Language :
- English
- ISSN :
- 0300483X
- Volume :
- 505
- Database :
- Academic Search Index
- Journal :
- Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 177603439
- Full Text :
- https://doi.org/10.1016/j.tox.2024.153843