Circ-Foxo3 is positively associated with the Foxo3 gene and leads to better prognosis of acute myeloid leukemia patients

Abstract

Background The Foxo3 gene, belonging to the forkhead family, is one of the classes of transcription factors characterized by a forkhead DNA-binding domain, which usually considered being a cancer suppressor gene. Circ-Foxo3 is a circular structure which connects the 3’end to the 5’end. Scholars detected that circ-Foxo3 could compete with Foxo3 for binding to some miRNAs. Methods In this study, we will test the expression of Foxo3 and circ-Foxo3 in de novo acute myeloid leukemia (AML) patients to explore the relationship between Foxo3 gene and circ-Foxo3. All the de novo AML samples and normal control samples was measured by real-time quantitative PCR. A receiver operating characteristic curve was conducted to differentiate AML patients from control people. Association of Foxo3 expression and overall survival was conducted by Kaplan-Meier survival analysis. Results We found that the expression of Foxo3 gene in de novo patients was significantly lower than control samples (P = 0.009). Meanwhile, circ-Foxo3 also expressed lower in de novo AML patients than in control samples (P = 0.040). In different classifications, this trend could be observed more remarkably. In non-M3 patients, the Foxo3 high patients’ survival time was longer than Foxo3 low patients (P = 0.002). Besides, in non-favorable risk groups, patients with low expression of Foxo3 had longer survival time than Foxo3 high patients (P = 0.004). Furthermore, in normal Karyotypic patients, the overall survival time of patients with high-expressed Foxo3 was significantly longer than those with low expression (P = 0.034). Besides, Pearson analysis was also conducted between these two genes in AML patients. Results revealed that they were positively correlated (R = 0.63, P < 0.001). Conclusion In conclusion, we found that low expression of circ-Foxo3 and Foxo3 were frequent in AML patients, and patients with high expression of Foxo3 often had a trend of better prognosis.

CircRNAs Dysregulated in Juvenile Myelomonocytic Leukemia: CircMCTP1 Stands Out

“…Few studies have investigated circRNA expression in myeloid malignancies. In acute myeloid leukemia (AML), a role for circRNAs in the regulation of cell proliferation and leukemogenesis ( Guarnerio et al, 2016 ; Sun et al, 2019 ; Yi et al, 2019 ), in drug resistance ( Shang et al, 2019b ; Cao et al, 2020 ), and as a diagnostic biomarker ( Zhou et al, 2019 ) has been reported. Furthermore, mounting evidence suggests a role as potential therapeutic targets ( Conn et al, 2015 ; Hirsch et al, 2017 ; Wu et al, 2018b ; Bell et al, 2019 ; Shang et al, 2019a , b ).…”

Circ_0000005 Facilitates Proliferation, Apoptosis, Migration and Invasion of Acute Myeloid Leukemia Cells via Modulating miR-139-5p/Tspan3 Axis

“…CircRNA-DLEU2 serves as an oncogenic circRNA in the AML progression via promoting PRKACB expression (29). Circ-Foxo3 is in positive association with the Foxo3 gene expression and its high expression contributes to a better prognosis of AML patients (30). In this study, we rst proved that circ_0000005 expression was greatly elevated in AML.…”

<p>Biological Roles and Mechanisms of Circular RNA in Human Cancers</p>

“…Circ-Foxo3 might be a promising biomarker for the prognosis and treatment of AML. 233 In addition, some circRNAs might be related to drug resistance in acute myeloid leukemia. For example, silence of circPAN3 significantly restored drug sensitivity to ADM in the two ADM-resistant cell lines, and overexpression of circPAN3 had the opposite effect.…”