A Potential ceRNA Network for Neurological Damage in Preterm Infants.

Jin Huang,Zhenyu Cai,Xuejing Liang,Yuzhen Xu

doi:10.1155/2021/2628824

Jin Huang, Zhenyu Cai + Show 2 more

Open Access

https://doi.org/10.1155/2021/2628824

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Abstract

Objective This study is aimed at identifying key genes involved in neurological damage in preterm infants and at determining their potential circRNA-miRNA-mRNA regulatory mechanisms. Methods Differentially expressed miRNAs, mRNAs, and circRNAs were downloaded from the GEO database. GO and KEGG enrichment analyses were used to determine possible relevant functions of differentially expressed mRNAs. The TTRUST database was used to predict differential TF-mRNA regulatory relationships. Then, CircMIR, miRDB, TargetScan and miRTarBase were then used to map circRNA/miRNA-TF/mRNA interaction networks. Finally, GSEA enrichment analysis was performed on the core transcription factors. Results A total of 640 mRNAs, 139 circRNAs, and 206 differentially expressed miRNAs associated with neurological injury in preterm infants were obtained. Based on the findings of Cytoscape and PPI network analysis, the hsa_circ_0008439-hsa-mir-3665-STAT3-MMP3 regulatory axis was established. GSEA analysis revealed that suppressed expression levels of STAT3 were associated with upregulated oxidative phosphorylation pathways in the neurological injury group of preterm infants. Conclusions The circRNA-miRNA-TF-mRNA regulatory network of neurological injury in preterm infants can be used to elucidate on the pathogenesis of brain injury and help us with the early detection of brain injury in preterm infants.

Highlights

Infants born at less than 37 weeks of gestational age are referred to as premature and often have a birth weight of less than 2500 g
The three datasets were used for the differential analysis of mRNA, miRNA, and circRNA, while the circRNA-miRNATF-mRNA network was constructed based on the results of database interactions
Peripheral blood miRNA expression matrices for 20 preterm and 50 nonpreterm pregnant women were downloaded from the GSE106224 dataset for miRNA analysis. circRNA expression data files for six preterm infants were downloaded from the GSE131475 dataset

Summary

Introduction

Infants born at less than 37 weeks of gestational age are referred to as premature and often have a birth weight of less than 2500 g. Due to the immaturity of their systemic organs, they are far more likely to suffer from complications when compared to full-term babies, especially neurological damage [1]. With advances in medical technology, the survival rates of preterm babies have significantly increased; incidences of neurological complications have not exhibited a proportional decrease [7]. Mechanisms involved in the development of neurological damage in preterm infants have not been elucidated. Studies have evaluated the roles of inflammatory factors [8], oxidative stress [9], and the amino acid accumulation [10], in the molecular mechanisms of neurological damage; findings have not been conclusive. Elucidation of the molecular mechanisms involved in neurological damage in preterm infants will inform the development of appropriate diagnostic and therapeutic options

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Discussion

Conclusion