Recognition of the Possible miRNA-mRNA Controlling Network in Stroke by Bioinformatics Examination

Abstract

Background. Based on the latest research of WHO, it has been revealed that more than 15 million people suffer from stroke every year worldwide. Of these 15 million people, 6 million succumb to death, and 5 million get permanently disabled. This is the prime reason for the substantial economic burden on all parts of the world. Methods. These data have been obtained from the GEO database, and the GEO2R tool was used to find out the differentially expressed miRNAs (DEMs) between the stroke and normal patients’ blood. FunRich and miRNet were considered to find potential upstream transcription factors and downstream target genes of candidate EMRs. Next, we use GO annotation and KEGG pathway enrichment. Target genes were analyzed with the help of the R software. Then, the STRING database and Cytoscape software were used to conduct PPI and DEM-hub gene networks. Finally, GSE58294 was used to estimate the hub gene expressions. Results. Six DEMs in total were selected out from GSE95204 and GSE117064 datasets. 663 DEMs’ target genes were predicted, and NRF1, EGR1, MYC, YY1, E2F1, SP4, and SP1 were predicted as an upstream transcription factor for DEMs’ target genes. Target genes of DEMs were primarily augmented in the PI3K-Akt signaling pathway and p53 signaling pathway. The network construction of DEM hygiene is potentially modulated by hsa-miR-3591-5p, hsa-miR-548as-3p, hsa-miR-206, and hsa-miR-4503 hub genes which were found among the top 10 of the hub genes. Among the top 10 hub genes, justification of CTNNB1, PTEN, ESR1, CCND1, KRAS, AKT1, CCND2, CDKN1B, and MYCN was constant with that in the GSE58294 dataset. Conclusion. In summary, our research first constructs the miRNA-mRNA network in stroke, which probably renders an awakening purview into the pathogenesis and cure of stroke.

Bioinformatic analysis and clinical diagnostic value of hsa_circ_0004099 in acute ischemic stroke

“…KRAS is a member of the RAS subfamily [33]. KRAS is one of the TOP 10 hub genes of a stroke gene array, indicating that KRAS may be involved in the occurrence and development of stroke [34].…”

Competing endogenous RNA network analysis of the molecular mechanisms of ischemic stroke

“…Globally, stroke remained the second-leading cause of death and the third-leading cause of long-term disability [ 1 , 2 ]. Statistically, about 17 million stroke cases occur worldwide each year [ 3 ], of which 85–90% are ischemic strokes (IS) [ 4 ]. Three of four survivors suffer from neurological defect-related sequelae, such as hemiplegia, cognitive impairments, or dysphasia, significantly affecting their health and quality of life and creating heavy burdens for families and society in general [ 5 , 6 ].…”

“…Three of four survivors suffer from neurological defect-related sequelae, such as hemiplegia, cognitive impairments, or dysphasia, significantly affecting their health and quality of life and creating heavy burdens for families and society in general [ 5 , 6 ]. Patients usually require long-term rehabilitation after the acute phase and need to receive continuous community support and nursing home care, thereby implying heavy societal and familial burdens [ 3 ].…”

“…Long non-coding RNAs (lncRNAs) are also a kind of non-coding RNA with more than 200 nucleotides in length that regulate target gene expression by interacting directly with mRNAs as a transcriptional regulator, or by acting as competing endogenous RNAs (ceRNAs), for miRNAs [ 21 , 22 ] and have been implicated in the development of IS [ 3 , 23 ]. For example, the knockdown of NEAT1 can significantly alleviate oxygen and glucose deprivation/reoxygenation (OGD/R) injury in neuronal cells by inhibiting an inflammatory response via the miR-374a 5p/NFAT5 axis [ 24 ].…”

“…As an important class of pervasive genes, several studies have found that non-coding RNAs (ncRNAs) play a key role in IS-induced neuroinflammation and iron overload [16][17][18]. MicroRNAs (MiRNAs) are 18-25-nucleotide-length noncoding RNA molecules that can regulate gene expression by destabilizing messenger RNA (mRNA) transcripts and inhibiting their shift into proteins [3,19]. Li et al demonstrated that upregulation of miR-103a-3p can alleviate inflammation, suppress cerebral ischemia-reperfusion injury, and exert neuroprotective effects [19].…”