Question

Identification of key microRNAs and the underlying molecular mechanism in spinal cord ischemia-reperfusion injury in rats

Answer 1

The underlying molecular processes for 19 important DE miRNAs in the etiology of SCII were confirmed. The DE miRNAs could serve as potential intervention targets for SCII. Additionally, blocking microRNAs-3568 reduced apoptosis and preserved hind limb function after SCII, possibly via modulating GATA6, GATA4, and RBPJ in SCII.

microRNAs:

• Short non-coding RNAs called miRNAs (microRNAs) control post-transcriptional gene expression.

• SCII (spinal cord ischemia-reperfusion damage) is a medical condition that can lead to paralysis and paraplegia, among other serious effects. The development of SCII is influenced by aberrant microRNAs expression. Different microRNAs expression results could be caused by variations in the experimenters, filtering circumstances, control choice, and sequencing platform.
• The purpose of this study is to investigate the important differently expressed microRNAs (DE miRNAs) and the underlying molecular mechanism in SCII by methodically analyzing the available SCII microRNAs expression data. A thorough bioinformatics study of 23 representative rat SCII miRNA datasets from PubMed was carried out. On mi RDB, the target genes of important DE miRNAs were predicted.
• Functional enrichment and transcription factor binding analyses using the DAVID and T Fact S databases. Nine were increased (miR-144-3p, miR-3568, miR-204, miR-30c, miR-34c-3p, miR-155-3p, miR-200b, miR-463, and miR-760-5p) and ten were downregulated (this study found 19 important DE miRNAs involved in SCII) (miR-28-5p, miR-21-5p, miR-702-3p, miR-291a-3p, miR-199a-3p, miR-352, miR-743b-3p, miR-125b-2-3p, miR-129-1-3p, and miR-136).Target genes of the increased DE miRNAs underwent KEGG enrichment analysis, which identified the pathways primarily involved as being the cGMP-PKG and cAMP signaling pathways. According to KEGG enrichment analysis of the downregulated DE miRNAs' target genes, the main signaling pathways involved were the Chemokine and MAPK signaling pathways. The target genes of the increased DE miRNAs were clearly enriched in biological processes such brain development and the positive control of transcription from RNA polymerase II promoter, according to GO enrichment analysis.
• The majority of the target genes of the downregulated DE miRNAs were enriched in biological processes such intracellular signal transmission and the inhibition of cell growth. The transcription factor study revealed that the four transcription factors, SP1, GLI1, GLI2, and FOXO3, had significant regulatory effects on the main DE miRNAs' target genes. MiR-3568 stood out among the elevated DE miRNAs as being particularly intriguing. SCII results in significant neurological deficiencies in the lower extremities, but miR-3568 anti-miRNA oligonucleotides (AMOs) enhance neurological performance. When compared to the sham group, cleaved caspase-3 and Bax were significantly elevated in SCII, however the overexpression was inhibited by miR-3568 AMO. In contrast to cleaved caspase-3, Bcl-2 expression levels exhibited a pattern. Following the attenuation of this increase by SCII and microRNAs-3568 AMO, the expression of GATA6, GATA4, and RBPJ reduced.

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