慢性钴暴露诱导人大脑类器官神经毒性的ceRNA调控机制

doi:10.3969/j.issn.1004-616x.2025.06.004

Abstract

Abstract: OBJECTIVE：Based on whole transcriptome sequencing and co-expression analysis，this study aimed to explore changes in non-coding RNA (ncRNA) expression profiles under chronic cobalt exposure to cerebral organoids and to investigate the role of competitive endogenous RNA (ceRNA) network in cobalt-induced neurotoxicity. METHODS：Mature cerebral organoids were continuously exposed to 0 and 20 μmol/L CoCl₂ for 28 days. Whole transcriptome sequencing was performed using the NovaSeq X Plus platform. Differential genes and differential ncRNAs between the control group and cobalt exposure group were identified with the screening thresholds of [log₂FC]≥1 and P_adjust<0.05，followed by gene ontology (GO) enrichment analysis. CeRNAs with potential interactions were screened according to Spearman correlation coefficient to construct a ceRNA network. Some RNAs in the network were verified by real-time quantitative PCR (RT-qPCR). RESULTS：A total of 2 968 differential genes，2 832 differential lncRNAs，82 differential miRNAs，and 35 differential circRNAs were identified by whole transcriptome sequencing. GO analysis showed that differential genes and target genes of differential ncRNAs were associated with metabolites and energy production，mainly including ATP biosynthesis，mitochondrial respiratory chain complex，and electron transport chain. Further verification using iPSC-derived neurons indicated that cobalt exposure could reduce intracellular ATP synthesis. Finally，a ceRNA regulatory network specific to the energy metabolism gene set was constructed，including 11 mRNAs，10 miRNAs，30 lncRNAs，and 2 circRNAs. RT-qPCR verification showed that the expression trends of PKM and miRNA 17_9658 were opposite，which was consistent with the sequencing results. CONCLUSION：Chronic cobalt exposure may induce neurotoxicity by affecting metabolic pathways，and the ceRNA regulatory network may play an important role in the neurotoxic mechanism of heavy metal cobalt.

Key words: cobalt, cerebral organoids, whole transcriptome sequencing, ceRNA network

CLC Number:

R3
R994.6

GUO Xinhua, HUANG Yan, CHEN Qiqi, LU Shiya, ZENG Pinli, WANG Zhiqiu, LI Hao, BU Qian. ceRNA regulatory mechanisms in neurotoxicity induced by chronic cobalt exposure in cerebral organoids[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2025, 37(6): 445-451,457.

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ceRNA regulatory mechanisms in neurotoxicity induced by chronic cobalt exposure in cerebral organoids

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