lncRNA FTX regulates acute hypoxia-induced synaptic vesicle injury in hippocampal neurons via the miR-137-3p/ SNAREs pathway
- VernacularTitle:lncRNA FTX调控miR-137-3p对急性低氧暴露海马神经元突触囊泡SNAREs复合体影响的分子机制
- Author:
Qi FU
1
;
Yu WANG
2
;
Honggang CHEN
2
;
Ruili GUAN
2
;
Yuankang ZOU
2
;
Chong XUE
2
;
Kejun DU
1
Author Information
- Publication Type:Specialtopic:Extremeenvironmentsandhealth
- Keywords: acute hypoxia exposure; human hippocampal neuronal cell; lncRNA FTX; miR-137-3p; synaptosomal-associated protein 25; synaptic vesicle cycle
- From: Journal of Environmental and Occupational Medicine 2026;43(9):1059-1068
- CountryChina
- Language:Chinese
- Abstract: Background Acute hypoxia exposure can impair synaptic transmission in hippocampal neurons and disrupt neural network function. However, the specific molecular mechanisms underlying hypoxia-induced synaptic vesicle dysfunction remain not fully elucidated. Objective To investigate the molecular mechanisms underlying acute hypoxia-induced synaptic vesicle dysfunction in human hippocampal neuronal cells (HPPNCs) with a particular focus on the regulatory role of long non-coding RNA (lncRNA) FTX in the miR-137-3p/soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex axis. Methods An acute hypoxia injury model was established in HPPNCs. Cell counting kit-8 (CCK-8) assay was used to determine the optimal seeding density and hypoxic exposure duration. Proteomic analysis was utilized to identify differentially expressed proteins (DEPs) between normoxic and hypoxic conditions, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to identify affected biological pathways. Bioinformatics prediction (e.g, RPISeq prediction of RNA-protein interactions) was integrated with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting to evaluate changes in DEPs and the lncRNA FTX/miR-137-3p axis. Small interfering RNA (siRNA) silencing and interaction potential prediction were further employed to confirm the regulatory role of lncRNA FTX. Results CCK-8 assay determined that the optimal seeding density for HPPNCs was 3.5×103 cells·well−1 and that 48 h of acute hypoxia exposure significantly reduced cell viability. Proteomic analysis revealed that DEPs were primarily enriched in the synaptic vesicle cycle pathway. Synaptosomal-associated protein 25 (SNAP25), a core component of the SNARE complex, was significantly downregulated at both mRNA and protein levels (P < 0.01). Mechanistic studies found that lncRNA FTX expression was significantly decreased in hypoxic cells, whereas miR-137-3p expression was significantly elevated. Furthermore, siRNA silencing of lncRNA FTX significantly reduced SNAP25 expression. RPISeq prediction suggested a potential interaction between lncRNA FTX and the SNAP25 protein (random forest, RF=0.75; support vector machine, SVM=0.56). Conclusion Acute hypoxia exposure may impair synaptic vesicle function in hippocampal neuronal cells by downregulating lncRNA FTX, increasing miR-137-3p expression, and suppressing SNAP25 expression, thereby disrupting the SNARE complex. These findings suggest that the lncRNA FTX/miR-137-3p/SNAP25 axis may play an important role in acute hypoxia-induced synaptic dysfunction.
