医学分子生物学杂志 ›› 2022, Vol. 19 ›› Issue (5): 366-373.doi: 10.3870/j.issn.1672-8009.2022.05.003

• 论著 • 上一篇    下一篇

lncRNA HOXB-AS3 通过激活 PI3K-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 

  

  1. 厦门大学附属第一医院1血液科, 2普外科 福建省厦门市, 361003
  • 出版日期:2022-09-30 发布日期:2023-01-13

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

  1. 1 Department of Hematology, 2 Department of General Surgery, the First Affiliated Hospital of Xiamen University, Xiamen, Fujian, 361003, China
  • Online:2022-09-30 Published:2023-01-13

摘要: 目的 探究 lncRNA HOXB-AS3 对急性髓样白血病 (acute myeloid leukemia, AML) 的增殖、 凋亡 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 HOXB-AS3 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-HOXB-AS3-03 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、 VEGF、 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、 凋亡和侵袭。

关键词: lncRNA HOXB-AS3, 急性髓样白血病, 增殖, 凋亡, 侵袭, PI3K-AKT 通路

Abstract: 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 blotting 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 lncRNA 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, PI3Kp85α and p-AKT. The low expression of HOXB-AS3 significantly inhibited the tumor growth, and down-regulated the expression level of PI3Kp85α and p-AKT In vivo. Conclusion lncRNA HOXB-AS3 aggravates the proliferation, apoptosis and invasion of AML cells by activating the PI3K-AKT pathway.

Key words: lncRNA HOXB-AS3, acute myeloid leukemia, proliferation, apoptosis, invasion, PI3K-AKT pathway 

中图分类号: