Wu Z J, Sun Q, Gu D L, Wang L Q, Li J Y, Jin H
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial People Hospital), Nanjing 210029, China.
Zhonghua Xue Ye Xue Za Zhi. 2021 Mar 14;42(3):230-237. doi: 10.3760/cma.j.issn.0253-2727.2021.03.009.
To explore the expression of circ-KEL in patients with acute myeloid leukemia (AML) and the effect and mechanism of circ-KEL on leukemic cells. The expression of circ-KEL was detected by quantitative real-time polymerase chain reaction in bone marrow mononuclear cells collected from 116 patients with AML and 40 healthy donors. The correlation of circ-KEL expression with the clinical characteristics of patients with AML was further systematically analyzed. The modulations among circ-KEL, miR-335-5p, and LRG1 were predicted through bioinformatics analysis and validated by dual luciferase assay. Cell proliferation and apoptosis were detected using CCK8 and flow cytometry. The expression of circ-KEL was significantly elevated in patients with AML compared with the healthy controls (Relative expression level, -Δct, AML: -7.117±1.831; control: -8.669±1.771, <0.001) . Moreover, patients with high circ-KEL expression have significantly worse overall survival. The level of circ-KEL in patients with AML was downregulated after chemo-treatment. In addition, circ-KEL could serve as the sponge of miR-335-5p and regulate LRG1. Bioinformatics analysis showed that miR-335-5p correlates with good prognosis and was negatively associated with LRG1. LRG1 could promote cell proliferation and inhibit cell apoptosis. Our results also exhibited the higher expression of LRG1 in patients with AML. Moreover, circ-KEL exerted functional effects via sponging miR-335-5p and regulating LRG1. circ-KEL expresses highly in patients with AML and correlates with poor prognosis, suggesting its important role in the genesis and progress of AML.
探讨环状KEL(circ-KEL)在急性髓系白血病(AML)患者中的表达及其对白血病细胞的作用和机制。采用定量实时聚合酶链反应检测116例AML患者和40例健康供者骨髓单个核细胞中circ-KEL的表达。进一步系统分析circ-KEL表达与AML患者临床特征的相关性。通过生物信息学分析预测circ-KEL、miR-335-5p和富含亮氨酸α-2糖蛋白1(LRG1)之间的调控关系,并通过双荧光素酶报告基因实验进行验证。使用CCK8和流式细胞术检测细胞增殖和凋亡。与健康对照相比,AML患者中circ-KEL的表达显著升高(相对表达水平,-Δct,AML:-7.117±1.831;对照:-8.669±1.771,<0.001)。此外,circ-KEL高表达的患者总生存期明显更差。化疗后AML患者的circ-KEL水平下调。此外,circ-KEL可作为miR-335-5p的海绵并调节LRG1。生物信息学分析显示,miR-33