Long noncoding RNA Sh2d3c promotes manganese-induced neuronal apoptosis through the mmu-miR-675-5p/Chmp4b/Bax axis

Wenmin Lu; Danni Li; Shengtao Wei; Jie Yang; Chuanqiao Tang; Xiaoli Ma; Yunfeng Zou

doi:10.1016/j.toxlet.2022.06.002

Long noncoding RNA Sh2d3c promotes manganese-induced neuronal apoptosis through the mmu-miR-675-5p/Chmp4b/Bax axis

Toxicol Lett. 2022 Jul 15:365:24-35. doi: 10.1016/j.toxlet.2022.06.002. Epub 2022 Jun 8.

Authors

Wenmin Lu¹, Danni Li¹, Shengtao Wei¹, Jie Yang¹, Chuanqiao Tang¹, Xiaoli Ma¹, Yunfeng Zou²

Affiliations

¹ Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China; Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China.
² Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China; Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, Guangxi, China; Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China. Electronic address: zouyunfeng@gxmu.edu.cn.

PMID: 35690225
DOI: 10.1016/j.toxlet.2022.06.002

Abstract

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-miR-675-5p 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.

Keywords: Apoptosis; LncRNA; Manganese; MiRNA; Neurotoxicity.

MeSH terms

Animals
Apoptosis / genetics
Cell Proliferation
Endosomal Sorting Complexes Required for Transport* / genetics
Manganese / toxicity
Mice
MicroRNAs* / genetics
Neurons* / drug effects
Neurons* / metabolism
RNA, Long Noncoding* / genetics
bcl-2-Associated X Protein* / genetics

Substances

Bax protein, mouse
CHMP4B protein, mouse
Endosomal Sorting Complexes Required for Transport
MIRN675 microRNA, mouse
MicroRNAs
RNA, Long Noncoding
bcl-2-Associated X Protein
Manganese