Effects of SIDT2 on the miR-25/NOX4/HuR axis and SIRT3 mRNA stability lead to ROS-mediated TNF-α expression in hydroquinone-treated leukemia cells.

Autor: Wang LJ; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan., Lee YC; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan., Chiou JT; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan., Chen YJ; Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, 807, Taiwan., Chang LS; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan. lschang@mail.nsysu.edu.tw.; Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. lschang@mail.nsysu.edu.tw.
Jazyk: angličtina
Zdroj: Cell biology and toxicology [Cell Biol Toxicol] 2023 Oct; Vol. 39 (5), pp. 2207-2225. Date of Electronic Publication: 2022 Mar 18.
DOI: 10.1007/s10565-022-09705-5
Abstrakt: Our previous studies indicated that the benzene metabolite hydroquinone (HQ) evokes the ROS/p38 MAPK/protein phosphatase 2A/tristetraprolin axis, leading to increased TNF-α expression in human acute myeloid leukemia cell lines U937 and HL-60. In this study, we aimed to identify the upstream pathway involved in ROS-mediated TNF-α expression. HQ treatment increased SIDT2 expression, which subsequently decreased miR-25 and SIRT3 expression in U937 cells. Notably, miR-25 downregulation promoted SIDT2 expression in HQ-treated U937 cells. SIDT2 induced lysosomal degradation of SIRT3 mRNA, but inhibited miR-25 expression through a lysosome-independent pathway. MiR-25 inhibition reduced NOX4 mRNA turnover, resulting in increased NOX4 protein levels. NOX4 induces mitochondrial ROS production and HuR downregulation. Restoration of HuR expression increased SIRT3 expression, suggesting that NOX4-mediated HuR downregulation promotes SIDT2-mediated degradation of SIRT3 mRNA. Inhibition of NOX4 or SIRT3 overexpression abolished HQ-induced ROS production, thereby abolishing TNF-α upregulation. Overall, these results indicate that SIDT2 regulates the miR-25/NOX4/HuR axis and SIRT3 mRNA destabilization, leading to ROS-mediated TNF-α upregulation in HQ-treated U937 cells. HQ-induced increase in TNF-α expression in HL-60 cells was also mediated through a similar pathway.
(© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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