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Research Paper

Effect of circRNA_FOXO3 rs12196996 polymorphism and FOXO3 rs2232365 polymorphism on survival rate and severity of intensive care unit-acquired sepsis

, , , , , & ORCID Icon show all
Pages 4821-4831 | Received 14 Oct 2021, Accepted 21 Jan 2022, Published online: 13 Feb 2022

Figures & data

Table 1. Basic characteristics of recruited patients

Figure 1. Differential expression of circRNA_FOXO3, miR-23a and FOXO3 mRNA in the peripheral blood of patients with ICU-acquired sepsis (one-way ANOVA and Tukey’s test, * P value < 0.05 vs. Group 1).

A: Cox regression models for survival analysis found that rs12196996 GG + rs2232365 AA was correlated with increased survival of patients with ICU-acquired sepsis than rs12196996 AA/AG + rs2232365 GG/GA.B: RT-PCR analysis found that rs12196996 GG was correlated with decreased expression of circRNA_FOXO3 in the peripheral blood of patients with ICU-acquired sepsis when compared with rs12196996 AA/AG.C: RT-PCR analysis found that rs12196996 GG + rs2232365 AA was correlated with increased expression of miR-23a in the peripheral blood of patients with ICU-acquired sepsis when compared with rs12196996 AA/AG + rs2232365 GG/GA.D: RT-PCR analysis found that rs12196996 GG was correlated with decreased expression of circRNA_FOXO3 in the PBMCs of patients with ICU-acquired sepsis when compared with rs12196996 AA/AG.E: RT-PCR analysis found that rs12196996 GG + rs2232365 AA was correlated with increased expression of miR-23a in the PBMCs of patients with ICU-acquired sepsis when compared with rs12196996 AA/AG + rs2232365 GG/GA.F: RT-PCR analysis found that rs12196996 GG was correlated with decreased expression of FOXO3 mRNA in the PBMCs of patients with ICU-acquired sepsis when compared with rs12196996 AA/AG.
Figure 1. Differential expression of circRNA_FOXO3, miR-23a and FOXO3 mRNA in the peripheral blood of patients with ICU-acquired sepsis (one-way ANOVA and Tukey’s test, * P value < 0.05 vs. Group 1).

Figure 2. Differential expression of IL-10, TNF, IL-2 and IFN in the peripheral blood of patients with ICU-acquired sepsis (one-way ANOVA and Tukey’s test, * P value < 0.05 vs. Group 1).

A: ELISA analysis found that rs12196996 GG + rs2232365 AA was correlated with increased expression of IL-10 in the PBMCs of patients with ICU-acquired sepsis when compared with rs12196996 AA/AG + rs2232365 GG/GA.B: ELISA analysis found that rs12196996 GG + rs2232365 AA was correlated with decreased expression of TNF in the PBMCs of patients with ICU-acquired sepsis when compared with rs12196996 AA/AG + rs2232365 GG/GA.C: ELISA analysis found that rs12196996 GG + rs2232365 AA was correlated with decreased expression of IL-2 in the PBMCs of patients with ICU-acquired sepsis when compared with rs12196996 AA/AG + rs2232365 GG/GA.D: ELISA analysis found that rs12196996 GG + rs2232365 AA was correlated with decreased expression of IFN in the peripheral blood lymphocytes of patients with ICU-acquired sepsis when compared with rs12196996 AA/AG + rs2232365 GG/GA.E: ELISA analysis found that rs12196996 GG + rs2232365 AA was correlated with decreased expression of IL-6 in the PBMCs of patients with ICU-acquired sepsis when compared with rs12196996 AA/AG + rs2232365 GG/GA.F: ELISA analysis found that rs12196996 GG + rs2232365 AA was correlated with decreased expression of IL-1β in the peripheral blood lymphocytes of patients with ICU-acquired sepsis when compared with rs12196996 AA/AG + rs2232365 GG/GA.
Figure 2. Differential expression of IL-10, TNF, IL-2 and IFN in the peripheral blood of patients with ICU-acquired sepsis (one-way ANOVA and Tukey’s test, * P value < 0.05 vs. Group 1).

Figure 3. miR-23a suppressed the expression of circRNA_FOXO3 and FOXO3 (* P value < 0.05 vs. control group).

A: Sequence analysis and luciferase assay indicated that miR-23a repressed the luciferase activity of wild type circRNA_FOXO3 (one-way ANOVA and Tukey’s test).B: Sequence analysis and luciferase assay indicated that miR-23a repressed the luciferase activity of wild type FOXO3 (one-way ANOVA and Tukey’s test).C: RT-PCR analysis indicated that miR-23a precursors suppressed the expression of circRNA_FOXO3 in HUVECs cells (student’s t-test).D: RT-PCR analysis indicated that miR-23a precursors activated the expression of miR-23a in HUVECs cells (student’s t-test).E: RT-PCR analysis indicated that FOXO3 siRNA suppressed the expression of FOXO3 mRNA in HUVECs cells (student’s t-test).
Figure 3. miR-23a suppressed the expression of circRNA_FOXO3 and FOXO3 (* P value < 0.05 vs. control group).

Figure 4. CircRNA_FOXO3 siRNA and FOXO3 siRNA restored the LPS induced dys-regulation of TNF-α, IL-1β, IL-6, miR-23a, circRNA_FOXO3 and FOXO3 (one-way ANOVA and Tukey’s test, * P value < 0.05 vs. NC group; ** P value < 0.05 vs. LPS+NC siRNA).

A: CCK-8 assay results indicated that the LPS induced cell viability loss of HUVECs cells was restored by circRNA_FOXO3 siRNA and FOXO3 siRNA.B: ELISA analysis indicated that the LPS induced TNF-α upregulation was restored by circRNA_FOXO3 siRNA and FOXO3 siRNA.C: ELISA analysis indicated that the LPS induced IL-1β upregulation was restored by circRNA_FOXO3 siRNA and FOXO3 siRNA.D: ELISA analysis indicated that the LPS induced IL-6 upregulation was restored by circRNA_FOXO3 siRNA and FOXO3 siRNA.E: RT-PCR analysis indicated that the LPS induced TNF-α mRNA upregulation was restored by circRNA_FOXO3 siRNA and FOXO3 siRNA.F: RT-PCR analysis indicated that the LPS induced IL-1β mRNA upregulation was restored by circRNA_FOXO3 siRNA and FOXO3 siRNA.G: RT-PCR analysis indicated that the LPS induced IL-6 mRNA upregulation was restored by circRNA_FOXO3 siRNA and FOXO3 siRNA.H: RT-PCR analysis indicated that the LPS induced decrease of miR-23a expression in HUVECs cells was restored by circRNA_FOXO3 siRNA and FOXO3 siRNA.I: RT-PCR analysis indicated that the LPS induced FOXO3 mRNA upregulation was restored by circRNA_FOXO3 siRNA and FOXO3 siRNA.J: RT-PCR analysis indicated that the LPS induced circRNA_FOXO3 upregulation was restored by circRNA_FOXO3 siRNA and FOXO3 siRNA.
Figure 4. CircRNA_FOXO3 siRNA and FOXO3 siRNA restored the LPS induced dys-regulation of TNF-α, IL-1β, IL-6, miR-23a, circRNA_FOXO3 and FOXO3 (one-way ANOVA and Tukey’s test, * P value < 0.05 vs. NC group; ** P value < 0.05 vs. LPS+NC siRNA).