SFPQ is involved in regulating arsenic-induced oxidative stress by interacting with the miRNA-induced silencing complexes. (June 2020)

• Record Type: Journal Article
• Authors: Guo, Ping; Chen, Shen; Li, Daochuan; Zhang, Jinmiao; Luo, Jiao; Zhang, Aihua; Yu, Dianke; Bloom, Michael S.; Chen, Liping; Chen, Wen
• Is Part Of: Environmental pollution. Volume 261(2020)
• Publication Date: 2020-06
• Subjects: Oxidative stress -- Arsenic -- SFPQ -- miRISC -- Oxidase and antioxidase; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2020.114160
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Arsenic exposure contributed to the development of human diseases. Arsenic exerted multiple organ toxicities mainly by triggering oxidative stress. However, the signaling pathway underlying oxidative stress is unclear. We previously found that the expression of SFPQ, a splicing factor, was positively associated with urinary arsenic concentration in an arsenic-exposed population, suggesting an oxidative stress regulatory role for SFPQ. To test this hypothesis, we established cell models of oxidative stress in human hepatocyte cells (L02) treated with NaAsO2 . Reactive oxygen species (ROS) synthesis displayed a time- and dose-dependent increase with NaAsO2 treatment. SFPQ suppression resulted in a 36%–53% decrease in ROS generation, leading to enhanced cellular damage determined by 8-OHdG, comet tail moment, and micronucleus analysis. Particularly, SFPQ deficiency attenuated expression of the oxidase genes DUOX1, DUOX2, NCF2, and NOX2. A fluorescent-based RNA electrophoretic mobility shift assay (FREMSA) and dual-luciferase reporter system revealed that miR-92b-5p targeted DUOX2 mRNA degradation. An RNA immunoprecipitation assay showed an interaction between SFPQ and miR-92b-5p of the miRNA-induced silencing complex (miRISC). Notably, NaAsO2 treatment diminished the interaction between SFPQ and miR92b-5p, accompanied by decreased binding between miR-92b-5p and 3′-UTR of DUOX2. However, SFPQ deficiency suppressed the dissociation of miR-92b-5p from 3′-UTR of DUOX2, indicating that miR-92b-5p regulated the SFPQ-dependent DUOX2 expression. Taken together, we reveal that SFPQ responds to arsenic-induced oxidative stress by interacting with the miRISC. These findings offer new insight into the potential role of SFPQ in regulating cellular stress response. Graphical abstract: Image 1 Highlights: SFPQ is involved in arsenic-induced oxidative stress. SFPQ regulated expression of oxidase genes by modulating SFPQ-miRISC complexes. SFPQ is a positive modulator of the cellular stress response.