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

Abstract

This study investigates the expression and effect of hsa_circ_0004099 in acute ischemic stroke (AIS). We conducted a case-controlled study that included 40 patients with AIS within 24 hours and 40 healthy subjects during the same period as a control group. Differentially expressed circular RNAs (circRNAs) were obtained using GEO2R, and the expression of hsa_circ_0004099 was verified using RT-PCR. Correlation analysis of the National Institutes of Health Stroke Scale (NIHSS) disease severity score and ischemic time with hsa_circ_0004099 expression levels was also performed. The receiver operating characteristic (ROC) curve of hsa_circ_0004099 was constructed, and bioinformatic analysis of hsa_circ_0004099 was performed. NIHSS scores negatively correlated with hsa_circ_0004099 levels (P<0.001, r = -0.7053), whereas infarct time was negatively correlated with hsa_circ_0004099 levels (P<0.001, r = -0.5130); hsa_circ_0004099 could benefit clinical diagnosis (area under the curve [AUC]: 0.923 [95% confidence interval [CI]: 0.8680–0.9904]). Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that hsa_circ_0004099 was enriched in several cancer pathways, which were collectively enriched in four genes namely TCF7L2, NRAS, CTNNB1, and KRAS. Eight core proteins were screened using a protein-protein interaction (PPI) network namely SMAD4, HIF1A, CTNNB1, CDKN1B, CDK6, FOXO3, KRAS, and NRAS. hsa_circ_0004099 is a potential clinical diagnostic marker. In addition, the possible role of hsa_circ_0004099 in the pathogenesis of AIS was analyzed using bioinformatics, which provided a new potential molecular target for AIS treatment.

Bioinformatics‐based analysis of mechanistic differences in vascular endothelial injury ischemic stroke induced by atrial fibrillation and atherosclerosis

“…Mutations that make RAS more active by impairing GTPase activity prolong downstream signaling, which is associated with cancer cell growth (Kramer‐Drauberg & Ambrogio, 2021). KRAS is one of the top 10 hub genes of the stroke gene array, so it may be involved in the occurrence and development of stroke (Zheng et al, 2022). Based on our results of the serum GTPase assay in the four groups of patients, we found that GTPase expression was down‐regulated in the AF and AF stroke groups but up‐regulated in the AS group.…”

“…Mutations that make RAS more active by impairing GTPase activity prolong downstream signaling, which is associated with cancer cell growth (Kramer-Drauberg & Ambrogio, 2021). KRAS is one of the top 10 hub genes of the stroke gene array, so it may be involved in the occurrence and development of stroke (Zheng et al, 2022).…”

Clinical Application of Circular RNAs as Biomarkers in Acute Ischemic Stroke

“…Results have shown that patients with AIS have lower expression levels of hsa_circ_0004099. The NIHSS score and stroke time were negatively correlated with hsa_circ_0004099 levels, suggesting its potential as therapeutic target in AIS [ 24 ].…”

The possible molecular mechanism underlying the involvement of the variable shear factor QKI in the epithelial-mesenchymal transformation of oesophageal cancer

“…Circular RNAs (circRNAs) have a unique covalent closed loop structure, so their stability is excellent, and their expression is relatively conserved. CircRNAs can participate in a variety of biological processes, among which circRNAs can regulate the expression of their downstream target genes through interactions with RNA-binding proteins [11][12][13]. The cyclic RNA-binding protein QKI is located on human chromosome 6.…”