Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis

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外文摘要：Objective:Acute myeloid leukemia(AML)is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion.Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis.In this study,we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition.Methods:Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls.A systematic analysis of clinical characteristics and prognostic factors was also conducted.Cell growth was assessed using the Cell Counting Kit-8(CCK-8)assay,and apoptosis and cell cycle progression were evaluated by flow cytometry.Moreover,RNA pull-down was performed to identify target microRNAs,and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets.Results:Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival(OS)(hazard ratio:2.357;95％confidence interval 1.258-4.415).The circ_0012152 knockdown reduced cell growth,increased apoptosis,and inhibited cell cycle progression in AML cell lines.RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152.Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors.We suggested that miR-652-3p targeted SOX4,as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells.Conclusion:Circ_0012152 is an independent poor prognostic factor for OS in AML,and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

外文关键词：

acute myeloid leukemiacirc_0012152miR-652-3pSOX4cell growth

作者：

Ying CHEN、Bi-xia LI、Ting-ting NIU、Shu-jun YANG、Li-chao WU、Le-huai SHI、Duo-bing ZOU、Ning-ning WU、Li-xia SHENG、Xiao YAN、Gui-fang OUYANG、Qi-tian MU

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作者单位：

Laboratory of Stem Cell Transplantation,The First Affiliated Hospital of Ningbo University,Ningbo,315300,China

Ningbo Clinical Research Center For Hematologic Malignancies,Ningbo,315300,China

Department of Hematology,The First Affiliated Hospital of Ningbo University,Ningbo,315300,China

School of Medicine,Hangzhou City University,Zhejiang University,Hangzhou,310000,China

Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,Ningbo,315300,China

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出版年：

2024

DOI：

10.1007/s11596-024-2878-y

当代医学科学(英文)

华中科技大学同济医学院

当代医学科学(英文)

影响因子：0.748

ISSN：2096-5230

年,卷(期)：2024.44(3)