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.pdf

（编校：闫沛）3359MODERNONO.31.No.182023年0 9 月第31卷第18 期现代肿瘤医学cell growth and apoptosis by targeting BCL2L11 in gastric cancerJ.Protein Cell,2016,7(2):141-151.8LIU R,ZHANG HY,WANG X,et al.The miR-24-Bim pathwaypromotes tumor growth and angiogenesis in pancreatic carcinomaJ.Oncotarget,2015,6(41):43831-43842.9YAN L,MA JZ,ZHU YP,et al.miR-24-3p promotes cell migra-tion and proliferation in lung cancer by targeting SOX7 J.J CellBiochem,2018,119(5):3989-3998.10 JAFFE N.Osteosarcoma:review of the past,impact on the future.The American experience J.Cancer Treat Res,2009,152:239-262.11CALIN GA,DUMITRU CD,SHIMIZU M,et al.Frequent deletionsand down-regulation of micro-RNA genes miR15 and miR16 at13q14 in chronic lymphocytic leukemia J.Proc Natl Acad SciUSA,2002,99:15524.12FLEMMING A.Heart failure:Targeting miRNA pathology in heartdisease J.Nat Rev Drug Discov,2014,13:336.13DI LEVA G,GAROFALO M,CROCE CM.MicroRNAs in cancerJ.Annu Rev Pathol,2014,9:287.14NITURE S,GADI S,QI Q,et al.MicroRNA-483-5p inhibitshepatocellular carcinoma cell proliferation,cell steatosis,and fi-brosis by targeting PPAR and TIMP2 J.Cancers(Basel),2023,15(6):1715.15JAVDANI H,MOLLAEI H,KARIMI F,et al.Review article epi-thelial to mesenchymal transition-associated microRNAs inbreast cancer J.Mol Biol Rep,2022,49(10):9963-9973.16DONG ZH,LIAO ZP,He YL,et al.Advances in the biologicalfunctions and mechanisms of miRNAs in the development of os-teosarcoma J.T e c h n o l C a n c e r Re s T r e a t,2 0 2 2,2 1:15330338221117386.17JAMAYRAN AK,OKSUZ BA,AFANASYEVA Y,et al.Prognosticrole of elevated miR-24-3p in breast cancer and its associationwith the metastatic process J.Oncotarget,2018,9(16):12868-12878.18WANG B,YAN LF,SHI WH,et al.CircRNA PVT1 promotes pro-liferation and chemoresistance of osteosarcoma cells via the miR-24-3p/KLF8 axis J.Int J Clin Oncol,2022,27(4):811-822.19WOODS AL,HALL PA,SHEPHERD NA,et al.The assessment ofproliferating cell nuclear antigen(PCNA)immunostaining in pri-mary gastrointestinal lymphomas and its relationship to histologicalgrade,S+G2+M phase fraction(flow cytometric analysis)andprognosis J.Histopathology,1991,19(1):21-27.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邢增文，王文芳，石丹妮?，李家威，姚琦，韩燕媚，张正义1海口市妇幼保健院，海南海口57 0 2 0 3；2 中国人民解放军联勤保障部队第92 8 医院检验科；3肿瘤内科，海南海口57 0 2 0 3【摘要】目的：探讨circRNA-BAX.3（h s a _c i r c _0 0 517 99）、c i r c RNA-BA X.11（h s a _c i r c _0 0 518 0 0）和miR-128、m i R-2 14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细胞增殖和调亡中的作用。方法：采用实时荧光定量PCR（q RT-PCR）检测外周血样本和AML细胞系中circRNA-BAX.3、c ir c RNA-BA X.11、m iR-12 8、m iR-2 14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调亡能力。通过双荧光素酶报告分析BAX3UTR和miR-128、m i R-2 14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调亡（P0.05）。本研究发现了circRNA-BAX.3、c i r c RNA-BA X.11、m i R-12 8 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调亡（P0.05），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细胞调亡。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。【关键词】急性髓细胞白血病;circRNA-BAX.3;circRNA-BAX.11;miR-128;miR-214;BAX【中图分类号】R733.71【文献标识码】AD0I:10.3969/j.issn.1672-4992.2023.18.005【文章编号】16 7 2-4992-（2 0 2 3)18-3359-0 7【收稿日期】2022-11-03【修回日期】2023-05-20【作者简介】邢增文（198 9一），男，海南海口人，主管检验师，主要从事分子诊断、生化免疫研究。【通信作者】韩燕媚（198 0），女，海南人，副主任医师，主要从事医学遗传、产前诊断工作。E-mail：42 8 4390 3 q q.c o mModern Oncology 2023,31(18):3359-3365acute3360.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邢增文，等Mechanical studies of the effects of circ-BAX.3 and circ-BAX.11 in inhibitingmyeloid leukemia cellsXING Zengwen,WANG Wenfang,SHI Danni,LI Jiawei,YAO Qi,HAN Yanmei,ZHANG Zhengyi33Haikou of the Maternal and Child Health Hospital,Hainan Haikou 570203,China;Department of Clinical Laboratory Examina-tion;Department of Internal Medicine-Oncology,the 928th Hospital of the Joint Logistics Support Force of the Chinese Peoples Libera-tion Army,Hainan Haikou 570203,China.【A b s t r a c t Objective:To explore the regulatory relationship between circRNA-BAX.3(hsa_circ_0051799),cir-cRNA-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 detectthe expression levels of circRNA-BAX.3,circRNA-BAX.11,miR-128,miR-214 and BAX in peripheral bloodsamples and cell lines.Western-blot(WB)was used to detect the expression level of BAX protein.CCK-8 andflow cytometry were used to detect cell proliferation and apoptosis.The target relationship between BAX 3UTR andmiR-128 and miR-214 was analyzed by dual luciferase report.Results:circRNA-BAX.3 and circRNA-BAX.11were down-regulated in AML samples and cells,and both can promote the proliferation of AML cells and inhibit cellapoptosis,and the difference was statistically significant(P0.05).This study found a co-regulatory network ofcircRNA-BAX.3,circRNA-BAX.11,miR-128,miR-214,and BAX.Further bioinformatics found that BAX wasthe target gene of miR-128 and miR-124.miR-128 and miR-214 can significantly down-regulate