CircBCL11B acts as a ceRNA to facilitate 1, 2-dichloroethane-induced astrocyte swelling via miR-29b-3p/AQP4 axis in SVG p12 cells. (1st May 2023)

• Record Type: Journal Article
• Authors: Zhong, Yizhou; Zhang, Bingli; Huang, Yuji; Du, Jiaxin; Liang, Boxuan; Li, Zhiming; Ye, Rongyi; Wang, Bo; Xian, Hongyi; Yang, Xifei; Rong, Weifeng; Guo, Xiang; Yang, Xingfen; Huang, Zhenlie
• Is Part Of: Toxicology letters. Volume 380(2023)
• Page Start: 40
• Page End: 52
• Publication Date: 2023-05-01
• Subjects: 1, 2-DCE 1, 2-dichloroethane -- 3-OMG 3-O-methylglucose -- ANOVA analysis of variance -- ceRNA competitive endogenous RNA -- circRNAs circular RNAs -- Cy5 cyanine5 -- DAPI 4', 6-diamidino-2-phenylindole -- DMEM Dulbecco's modified Eagle's medium -- DMSO dimethyl sulfoxide -- FBS fetal bovine serum -- FC fold change -- FISH fluorescence in situ hybridization -- FITC fluorescein isothiocyanate -- FPKM fragments per kilobase of transcript per million mapped fragments -- HEPES 4-(2-hydroxyerhyl) piperazine-1-erhanesulfonic acid -- LSD least significant difference -- miRNAs microRNAs -- mRNA messenger RNA -- Mut mutant-type -- ncRNAs non-coding RNAs -- PBS phosphate-buffered saline -- qRT-PCR quantitative reverse transcription-polymerase chain reactions -- SD standard deviation -- TEM transmission electron microscopy -- siRNAs small interfering RNAs -- WT wild-type; 1, 2-Dichloroethane -- Aquaporin 4 -- Astrocyte swelling -- Brain edema -- CircBCL11B -- MiR-29b-3p; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2023.04.003
• Languages: English
• ISSNs: 0378-4274

Abstract

Abstract: 1, 2-Dichloroethane (1, 2-DCE) is a pervasive environmental pollutant found in ambient and residential air, as well as ground and drinking water. Brain edema is the primary pathological consequence of 1, 2-DCE overexposure. We found that microRNA (miRNA)-29b dysregulation after 1, 2-DCE exposure can aggravate brain edema by suppressing aquaporin 4 (AQP4). Moreover, circular RNAs (circRNAs) can regulate the expression of downstream target genes through miRNA, and affect protein function. However, circRNAs' role in 1, 2-DCE-induced brain edema via miR-29b-3p/AQP4 axis remains unclear. To address the mechanism's bottleneck, we explored the circRNA-miRNA-mRNA network underlying 1, 2-DCE-driven astrocyte swelling in SVG p12 cells by circRNA sequencing, electron microscopy and isotope 3 H labeling combined with the 3-O-methylglucose uptake method. The results showed that 25 and 50 mM 1, 2-DCE motivated astrocyte swelling, characterized by increased water content, enlarged cell vacuoles, and mitochondrial swelling. This was accompanied by miR-29b-3p downregulation and AQP4 upregulation. We verified that AQP4 were negatively regulated by miR-29b-3p in 1, 2-DCE-induced astrocyte swelling. Also, circRNA sequencing highlighted that circBCL11B was upregulated by 1, 2-DCE. This was manifested as circBCL11B overexpression playing an endogenous competitive role via upregulating AQP4 by binding to miR-29b-3p, thus leading to astrocyte swelling. Conversely, circBCL11B knockdown reversed the 1, 2-DCE-motivated AQP4 upregulation and alleviated the cell swelling. Finally, we demonstrated that the circBCL11B was targeted to miR-29b-3p by fluorescence in situ hybridization and dual-luciferase reporter assay. In conclusion, our findings indicate that circBCL11B acts as a competing endogenous RNA to facilitate 1, 2-DCE-caused astrocyte swelling via miR-29b-3p/AQP4 axis. These observations provide new insight into the epigenetic mechanisms underlying 1, 2-DCE-induced brain edema. Highlights: 1, 2-DCE induces astrocyte swelling by increased water content. 1, 2-DCE induces astrocyte swelling by enlarged cell vacuoles. 1, 2-DCE causes downregulation of miR-29b-3p, upregulation of AQP4 and circBCL11B. AQP4 are negatively regulated by miR-29b-3p in 1, 2-DCE-induced astrocyte swelling. 1, 2-DCE motivates astrocyte swelling via circBCL11B/miR-29b-3p/AQP4 axis.