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

Jiao Zhou,Jing Zhang,Ling-Yu Zhou,Ling-Ling Zhai,Xi Tang,Zhao-Qun Deng,Jing Yi,Jun Qian,Yun Yun Yi,Jiang Lin

doi:10.1186/s12885-019-5967-8

Abstract

BackgroundThe 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.MethodsIn 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.ResultsWe 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).ConclusionIn 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.

Highlights

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
Patients and samples The bone marrow (BM) samples of experimental group were collected from patients in the Affiliated Hospital of Jiangsu University who were initially diagnosed with acute myeloid leukemia, while the control group were from healthy BM donors or patients with chest trauma
The diagnostic value of Foxo3 and circ-Foxo3 expression The diagnostic value of Foxo3 and circ-Foxo3 expression was analyzed by Receiver operating characteristic curve (ROC) curve

Summary

Introduction

The Foxo 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. It is acknowledged that AML is a malignant clonal disease which results from blocked differentiation and uncontrolled proliferation or accumulation of abnormal hematopoietic cells. The Foxo gene, belonging to the forkhead family, is one of the classes of transcription factors characterized by a forkhead DNA-binding domain. This family includes four genes: Foxo, Foxo, Foxo and Foxo, but the Foxo was widely studied. Researchers considered it as a longevity gene [9]

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Conclusion