Objective To screen out the differentially expressed(DE) RNAs in human neuroblastoma cells (SH-SY5Y) after manganese (Mn) exposure, to investigate the competing endogenous RNA (ceRNA) network and the key RNAs co-expressed in SH-SY5Y cells exposed to Mn and the cerebral cortex of patients with Parkinson's disease (PD), and to reveal the common potential molecular mechanism of Mn-induced neurotoxicity and PD.
Methods mRNAs, miRNAs and lncRNAs in Mn-exposed SH-SY5Y cells(500 μmol/L MnCl2 for 6 h) were detected using Agilent human expression microarrays and the differential expression (DE) genes were analyzed by R software. The starBase and miRTarBase databases were used to identify the interaction between miRNA-lncRNA and miRNA-mRNA, Cytoscape software was used to construct the ceRNA regulatory network, and a comparative analysis was performed based on the expression data of miRNAs in the frontal cortex of PD patients in GEO database GSE72962. GO functional enrichment and KEGG pathway analyses were performed for DE mRNAs.
Results A total of 177 DE lncRNAs, 112 DE miRNAs, and 6353 DE mRNAs were screened out in SH-SY5Y cells after Mn exposure. Based on the results of co-expression analysis and ceRNA regulatory mechanism, 20 lncRNAs, 14 miRNAs, and 27 mRNAs were eventually incorporated into the lncRNA-miRNA-mRNA regulatory network based on 65 pairs of interaction relationship. The expression of miR-124-3p and miR-371a-5p showed significant changes in neural cells after Mn exposure and the frontal cortex of PD patients. GO and KEGG enrichment analyses showed that ceRNAs were mainly enriched in the pathways of nervous system development, apoptotic signal regulation, oxidative stress reaction, autophagy and cell senescence.
Conclusion The ceRNA regulatory network plays an important role in Mn-induced neurotoxicity, and miR-124-3p and miR-371a-5p may be biomarkers for the diagnosis and treatment of manganism and PD.
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