lncRNA HOXB-AS3通过激活PI3 K-AKT通路加剧急性髓样白血病患者细胞的增殖、凋亡、迁移和侵袭  

lncRNA HOXB-AS3 Aggravates the Proliferation,Apoptosis,Migration and Invasion of Acute Myeloid Leukemia Cells by Activating the PI3K-AKT Pathway

作　　者：黄耘[1] 于永洋[2] 苏蕊[1] 王思力[1] HUANG Yun;YU Yongyang;SU Rui;WANG Sili(Department of Hematology,the First Affliated Hospital of Xiamen University,Xiamen,Fujian,361003,China;Department of General Surgery,the First Affliated Hospital of Xiamen University,Xiamen,Fujian,361003,China)

机构地区：[1]厦门大学附属第一医院血液科,福建省厦门市361003 [2]厦门大学附属第一医院普外科,福建省厦门市361003

出　　处：《医学分子生物学杂志》2022年第5期366-373,共8页Journal of Medical Molecular Biology

基　　金：福建省自然科学基金(No.2021J01120459)。

摘　　要：目的探究lncRNA HOXB-AS3对急性髓样白血病(acutemyeloidleukemia,AML)的增殖、调亡和侵袭的影响和机制。方法RT-qPCR检测AML患者骨髓单核细胞(BMMCs)和细胞系中lncRNA HOXBAS3相对表达量。慢病毒转染建立稳定表达shRNA-HOXB-AS3-01,shRNA-HOXB-AS3-02和shRNA-HOXBAS3-03的THP1和HL60细胞系。CCK-8实验、EdU实验、流式细胞术实验和Transwell实验分别检测THP1和HL60细胞活力、增殖、凋亡和侵袭能力,Western印迹检测蛋白相对表达量。建立裸鼠AML移植瘤模型,体内验证HOXB-AS3低表达对肿瘤生长的影响。结果lncRNA HOXB-AS3在AML患者BMMCs和细胞系中的表达量显著增加。在细胞实验中,HOXB-AS3低表达显著抑制THP1和HL60细胞活力、增殖和侵袭,增加细胞凋亡率,上调cleaved caspase-3、cleaved caspase-9和E-cadherin蛋白的表达,下调N-cadherin、VECF、PI3Kp85α和p-AKT蛋白的表达。在体内实验中,HOXB-AS3低表达显著抑制肿瘤生长,下调PI3Kp85α和p-AKT蛋白表达。结论lncRNA HOXB-AS3通过激活PI3K-AKT通路加剧AML细胞的增殖、调亡和侵袭。Objective To investigate the effect of lncRNA HOXB-AS3 on cell proliferation,apoptosis and invasion in acute myeloid leukemia(AML)and the underlying mechanism.Methods The expression level of lncRNA HOXB-AS3 in bone marrow mononuclear cells(BMMCs)of AML patients and the AML cell lines were detected by RT-qPCR.THP1 and HL60 cell lines stably expressed shRNA-HOXB-AS3-01,shRNA-HOXB-AS3-02 or shRNA-HOXB-AS3-03 were established by lentivirus transfection.CCK-8 assay,EdU assay,flow cytometry,and transwell assay were used to measure the cell viability,proliferation,apoptosis and invasion,Western bloting was employed to detect the protein levels.The AML nude mouse xenograft model was established to verify the effect of low expression level of HOXB-AS3 on the tumor growth in vivo.Results The expression level of IncRNA HOXB-AS3 in AML BMMCs and cell lines was increased significantly.The low expression of HOXB-AS3 significantly inhibited the cell viability,proliferation,and invasion of THP1 and HL60 cells,enhanced the apoptosis,up-regulated the expression levels of cleaved caspase-3,cleaved caspase-9 and E-cadherin,and down-regulated the expression levels of N-cadherin,VEGF,PI3Kp85αand p-AKT.The low expression of HOXB-AS3 significantly inhibited the tumor growth,and down-regulated the expression level of PI3Kp85αand p-AKT In vivo.Conclusion lncRNA HOXB-AS3 aggravates the proliferation,apoptosis and invasion of AML cells by activating the PI3K-AKT pathway.

关 键 词：lncRNA HOXB-AS3 急性髓样白血病 增殖 凋亡 侵袭 PI3K-AKT通路 

分 类 号：R733.71[医药卫生—肿瘤]