Journal
TOXICOLOGY LETTERS
Volume 365, Issue -, Pages 24-35Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2022.06.002
Keywords
Manganese; LncRNA; MiRNA; Neurotoxicity; Apoptosis
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Funding
- National Natural Science Founda-tion of China [81872658, 81673135]
- Guangxi Natural Science Foundation Innovation Research Team Project [2019GXNSFGA245002]
- Guangxi Natural Science Founda-tion [2018GXNSFDA050011]
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This study reveals the role of lncRNAs in Mn-induced neurotoxicity, identifying lncSh2d3c as a key regulatory factor that is involved in Mn-induced neuronal apoptosis through the mmu-miR-675-5p/Chmp4b/Bax pathway. This finding suggests a novel mechanism of Mn-induced neurotoxicity and highlights the potential of lncSh2d3c as a therapeutic target.
Environmental excessive manganese (Mn) exposure can cause neurotoxicity and neurodegenerative diseases. Long noncoding RNAs (lncRNAs) have been shown to affect the development of neurodegenerative diseases. However, whether lncRNAs are also linked to Mn-induced neurotoxicity has not been reported. In this study, we explored the role of lncRNAs in Mn-induced neurotoxicity and its mechanisms. LncSh2d3c was identified to be the significantly increased lncRNA in Mn-exposed N2a cells. Knockdown of lncSh2d3c increased the cell viability and inhibited cell apoptosis. Mechanistically, lncSh2d3c acted as a sponge for mmu-miR-675-5p, thereby preventing the inhibitory effect of mmu-miR-675-5p on Chmp4b. The binding potency of lncSh2d3c/mmu-miR675-5p and mmu-miR-675-5p/Chmp4b was verified by RNA antisense purification (RAP) and luciferase reporter assays. Furthermore, we also found that the lncSh2d3c/mmu-miR-675-5p/Chmp4b/Bax axis might be associated with the learning ability and memory of mice after Mn exposure. These results revealed a novel mechanism of Mn-induced neuronal apoptosis through the lncSh2d3c/mmu-miR-675-5p/Chmp4b/Bax axis and suggested that lncSh2d3c may act as a key regulatory factor in Mn-induced neurotoxicity.
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