Comprehensive Analysis of RNA Expression Profile Identifies Hub miRNA-circRNA Interaction Networks in the Hypoxic Ischemic Encephalopathy

Abstract

Hypoxic ischemic encephalopathy (HIE) is classified as a sort of serious nervous system syndrome that occurs in the early life period. Noncoding RNAs had been confirmed to have crucial roles in human diseases. So far, there were few systematical and comprehensive studies towards the expression profile of RNAs in the brain after hypoxia ischemia. In this study, 31 differentially expressed microRNAs (miRNAs) with upregulation were identified. In addition, 5512 differentially expressed mRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) were identified in HIE groups. Bioinformatics analysis showed these circRNAs and mRNAs were significantly enriched in regulation of leukocyte activation, response to virus, and neutrophil degranulation. Pathway and its related gene network analysis indicated that HLA − DPA1, HLA − DQA2, HLA − DQB1, and HLA − DRB4 have a more crucial role in HIE. Finally, miRNA-circRNA-mRNA interaction network analysis was also performed to identify hub miRNAs and circRNAs. We found that miR-592 potentially targeting 5 circRNAs, thus affecting 15 mRNA expressions in HIR. hsa_circ_0068397 and hsa_circ_0045698 were identified as hub circRNAs in HIE. Collectively, using RNA-seq, bioinformatics analysis, and circRNA/miRNA interaction prediction, we systematically investigated the differentially expressed RNAs in HIE, which could give a new hint of understanding the pathogenesis of HIE.

LncRNAs and CircRNAs as Strategies against Pathological Conditions Caused by a Hypoxic/Anoxic State

“…Particularly, the article suggested further research on hsa_circ_0045698 and hsa_circ_0068397 due to their high expression levels. These circRNAs were identified as being central in HIE, indicating a potential role of circRNAs HIE development through circRNA/miRNA interactions [150].…”

Diagnostic and Therapeutic Roles of the “Omics” in Hypoxic–Ischemic Encephalopathy in Neonates

“…In addition to the miRNA studies, there have been a few systematic studies on the expression profiles of other RNAs in HIE. Several differentially expressed microRNAs with upregulation were identified in addition to the differentially expressed mRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) [ 38 ]. A microarray study involving the reverse transcriptase PCR of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed the differential expression of 456 circRNAs in HIE, with 250 upregulated and 206 downregulated circRNAs in comparison to the controls [ 37 ].…”