Bioinformatics-based analysis reveals IDR-1018-mediated ceRNA regulation network for protective effect on hypoxia-ischemic brain injury in neonatal mice.

Activation of an innate immune response serves as a key, contributing factor in perinatal brain injury. The current study sought to evaluate the clinical significance of innate defense regulatory peptide 1018 (IDR-1018)-derived peptide mediating ceRNA regulation network as a biomarker in neonatal mice with hypoxic-ischemic brain damage (HIBD). Firstly, bioinformatics analyses were performed to screen the HIBD-related candidate genes, miRNAs, and lncRNAs. The StarBase, miRDB, and LncBase databases were retrieved to obtain the lncRNA-miRNA-mRNA network, which revealed the ceRNA regulatory network mediated by IDR-1018. Subsequently, RT-qPCR was adopted to determine the expression patterns of MIAT, miR-7a-5p, and Plp2 in neonatal mice with HIBD after treatment with IDR-1018. Moreover, the relationship among mRNA, miRNA, and lncRNA in primary hippocampal neurons was verified by means of dual-luciferase reporter assay and RIP assay. Initial findings demonstrated that Plp2, mmu-miR-7a-5p, and three lncRNAs (MIAT, XIST, and 1700020I14RIK) were related to HIBD. Moreover, IDR-1018 could relieve HIBD in neonatal mice. Plp2 and MIAT were down-regulated, while mmu-miR-7a-5p was up-regulated in the striatum, hippocampus, and cortical tissues of the neonatal mice with HIBD, whereas treatment with the IDR-1018 could revere these trends. Additionally, MIAT acted as a ceRNA of miR-7a-5p to elevate Plp2 expression. In conclusion, our findings highlighted that IDR-1018 relieved HIBD in neonatal mice via the MIAT/miR-7a-5p/Plp2 axis.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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