Experimental cell research · 2026
MT1E binds to LncRNA NEAT1 to regulate SLC39A14-mediated ferroptosis in the pathogenesis of aortic dissection.
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Xiao Changbo, Zheng Zihe, Li Mingliang, Yang Quanlin, Dai Xiaofu
Аннотация
BACKGROUND: Aortic dissection (AD) is a life-threatening vascular disease whose pathogenesis involves dysfunction of vascular smooth muscle cells (VSMCs) and cell death. This study aimed to investigate the role of the MT1E/LncRNA NEAT1/SLC39A14 axis in AD and its molecular mechanism in regulating ferroptosis.
METHODS: The correlation between ferroptosis and AD was evaluated using single-sample gene set enrichment analysis (ssGSEA). Weighted gene co-expression network analysis (WGCNA) based on the GSE153434 dataset was performed to identify key modules. Differentially expressed genes were screened through GO, KEGG enrichment analyses, and protein-protein interaction (PPI) network analysis. The functions and interactions of MT1E, LncRNA NEAT1, and SLC39A14 were validated using RT-PCR, Western Blot, immunohistochemistry, Co-IP assay, RIP assay, and luciferase reporter assays. A mouse model was constructed to evaluate the role of MT1E in AD pathological injury and ferroptosis.
RESULTS: AD was significantly associated with ferroptosis. WGCNA identified a blue module highly correlated with ferroptosis, and 236 differentially expressed genes were screened. MT1E, LncRNA NEAT1, and SLC39A14 were significantly upregulated in aortic tissues of AD patients. Knockdown of MT1E inhibited AngII-induced VSMC proliferation, migration, and ferroptosis, and restored the expression of VSMC phenotypic transformation markers. MT1E activates NEAT1 expression by forming a complex with YBX1, while MT1E activates NEAT1 through zinc ion release-mediated regulation of SFPQ and NONO. Besides, luciferase reporter assays demonstrated the direct binding of LncRNA NEAT1 to SLC39A14. Overexpression of LncRNA NEAT1 reversed the inhibitory effects of MT1E knockdown on VSMC proliferation, migration, and ferroptosis. Overexpression of SLC39A14 counteracted the effects of MT1E or LncRNA NEAT1 knockdown on VSMCs. Mouse model experiments validated the critical role of MT1E in AD pathological injury and ferroptosis.
CONCLUSION: This study reveals that MT1E plays a pivotal role in AD by targeting LncRNA NEAT1 to regulate SLC39A14-mediated ferroptosis. These findings provide novel insights into the molecular mechanisms of AD and offer potential therapeutic targets for related diseases.
METHODS: The correlation between ferroptosis and AD was evaluated using single-sample gene set enrichment analysis (ssGSEA). Weighted gene co-expression network analysis (WGCNA) based on the GSE153434 dataset was performed to identify key modules. Differentially expressed genes were screened through GO, KEGG enrichment analyses, and protein-protein interaction (PPI) network analysis. The functions and interactions of MT1E, LncRNA NEAT1, and SLC39A14 were validated using RT-PCR, Western Blot, immunohistochemistry, Co-IP assay, RIP assay, and luciferase reporter assays. A mouse model was constructed to evaluate the role of MT1E in AD pathological injury and ferroptosis.
RESULTS: AD was significantly associated with ferroptosis. WGCNA identified a blue module highly correlated with ferroptosis, and 236 differentially expressed genes were screened. MT1E, LncRNA NEAT1, and SLC39A14 were significantly upregulated in aortic tissues of AD patients. Knockdown of MT1E inhibited AngII-induced VSMC proliferation, migration, and ferroptosis, and restored the expression of VSMC phenotypic transformation markers. MT1E activates NEAT1 expression by forming a complex with YBX1, while MT1E activates NEAT1 through zinc ion release-mediated regulation of SFPQ and NONO. Besides, luciferase reporter assays demonstrated the direct binding of LncRNA NEAT1 to SLC39A14. Overexpression of LncRNA NEAT1 reversed the inhibitory effects of MT1E knockdown on VSMC proliferation, migration, and ferroptosis. Overexpression of SLC39A14 counteracted the effects of MT1E or LncRNA NEAT1 knockdown on VSMCs. Mouse model experiments validated the critical role of MT1E in AD pathological injury and ferroptosis.
CONCLUSION: This study reveals that MT1E plays a pivotal role in AD by targeting LncRNA NEAT1 to regulate SLC39A14-mediated ferroptosis. These findings provide novel insights into the molecular mechanisms of AD and offer potential therapeutic targets for related diseases.