circ-BAX.3和circ-BAX.11抑制急性髓细胞性白血病细胞作用的机制研究  

Mechanical studies of the effects of circ-BAX.3 and circ-BAX.11 in inhibiting acute myeloid leukemia cells

作　　者：邢增文 王文芳 石丹妮 李家威 姚琦 韩燕媚 张正义 XING Zengwen;WANG Wenfang;SHI Danni;LI Jiawei;YAO Qi;HAN Yanmei;ZHANG Zhengyi(Haikou of the Maternal and Child Health Hospital,Hainan Haikou 570203,China;Department of Clinical Laboratory Examination,the 928th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army,Hainan Haikou 570203,China;Department of Internal Medicine-Oncology,the 928th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army,Hainan Haikou 570203,China)

机构地区：[1]海口市妇幼保健院,海南海口570203 [2]中国人民解放军联勤保障部队第928医院检验科,海南海口570203 [3]中国人民解放军联勤保障部队第928医院肿瘤内科,海南海口570203

出　　处：《现代肿瘤医学》2023年第18期3359-3365,共7页Journal of Modern Oncology

摘　　要：目的:探讨circRNA-BAX.3(hsa_circ_0051799)、circRNA-BAX.11(hsa_circ_0051800)和miR-128、miR-214以及BAX在人急性髓系白血病(AML)细胞中的相互作用关系及其在AML细胞增殖和凋亡中的作用。方法:采用实时荧光定量PCR(qRT-PCR)检测外周血样本和AML细胞系中circRNA-BAX.3、circRNA-BAX.11、miR-128、miR-214和BAX-mRNA的表达水平。免疫印迹法(WB)检测BAX蛋白表达水平。采用CCK-8和流式细胞仪检测细胞的增殖和凋亡能力。通过双荧光素酶报告分析BAX 3’UTR和miR-128、miR-214之间的靶向关系。结果:circRNA-BAX.3和circRNA-BAX.11在AML组织和细胞中表达下调,且两者均可明显促进AML细胞的增殖及抑制细胞凋亡(P<0.05)。本研究发现了circRNA-BAX.3、circRNA-BAX.11、miR-128和miR-214以及BAX的共调节网络。生物信息学分析结果显示,BAX是miR-128和miR-124的靶基因。miR-128和miR-214能够明显下调BAX表达,促进细胞增殖并抑制细胞凋亡(P<0.05),而circ-BAX.3和circ-BAX.11通过结合miR-128和miR-214促进BAX表达并加速AML细胞凋亡。结论:circRNA-BAX.3和circRNA-BAX.11通过抑制miR-128和miR-214并促进BAX的表达来抑制AML的进展。Objective:To explore the regulatory relationship between circRNA-BAX.3(hsa_circ_0051799),circRNA-BAX.11(hsa_circ_0051800),miR-128,miR-214 and BAX in human acute myeloid leukemia(AML)cells proliferation and apoptosis.Methods:Real-time fluorescent quantitative PCR(qRT-PCR)was used to detect the expression levels of circRNA-BAX.3,circRNA-BAX.11,miR-128,miR-214 and BAX in peripheral blood samples and cell lines.Western-blot(WB)was used to detect the expression level of BAX protein.CCK-8 and flow cytometry were used to detect cell proliferation and apoptosis.The target relationship between BAX 3'UTR and miR-128 and miR-214 was analyzed by dual luciferase report.Results:circRNA-BAX.3 and circRNA-BAX.11 were down-regulated in AML samples and cells,and both can promote the proliferation of AML cells and inhibit cell apoptosis,and the difference was statistically significant(P<0.05).This study found a co-regulatory network of circRNA-BAX.3,circRNA-BAX.11,miR-128,miR-214,and BAX.Further bioinformatics found that BAX was the target gene of miR-128 and miR-124.miR-128 and miR-214 can significantly down-regulate BAX expression,promote cell proliferation and inhibit cell apoptosis(P<0.05),while circ-BAX.3 and circ-BAX.11 promote BAX by binding to miR-128 and miR-214 expresses and accelerates apoptosis in AML cells.Conclusion:circRNA-BAX.3 and circRNA-BAX.11 inhibit the progression of AML by inhibiting miR-128 and miR-214 and promoting the expression of BAX.

关 键 词：急性髓细胞白血病 circRNA-BAX.3 circRNA-BAX.11 miR-128 miR-214 BAX 

分 类 号：R733.71[医药卫生—肿瘤]