KMT2A通过lncRNA-HOTAIR激活Akt/mTOR信号通路影响AML细胞的生物学行为  

KMT2A Activates Akt/mTOR Signaling Pathway Through LncRNA-HOTAIR to Influence the Biological Behavior of AML Cells

作　　者：黄耘[1] 张爱丽 苏蕊[1] 张莉娟 邹榕 王思力[1,2] HUANG Yun;ZHANG Ai-Li;SU Rui;ZHANG Li-Juan;ZOU Rong;WANG Si-Li(Department of Hematology,The First Affiliated Hospital of Xiamen University,Xiamen 361003,Fujian Province,China;School of Clinical Medicine,Fujian Medical University,Fuzhou 350122,Fujian Province,China;School of Medicine,Xiamen University,Xiamen 361005,Fujian Province,China)

机构地区：[1]厦门大学附属第一医院血液科,福建厦门361003 [2]福建医科大学临床医学部,福建福州350122 [3]厦门大学医学院,福建厦门361005

出　　处：《中国实验血液学杂志》2022年第3期732-736,共5页Journal of Experimental Hematology

基　　金：厦门市医疗卫生指导性项目(3502Z20209015)。

摘　　要：目的:探讨急性髓系白血病细胞中赖氨酸甲基转移酶2A(KMT2A)的表达及其影响急性髓系白血病细胞增殖的分子机制。方法:免疫共沉淀实验检测KMT2A和长链非编码RNA-HOX转录反义RNA(lncRNA-HOTAIR)之间的结合,5-乙炔基-2′脱氧尿嘧啶核苷(EdU)实验检测急性髓系白血病细胞增殖。结果:KMT2A组PCR扩增信号明显强于阴性对照组和IgG组(P<0.01)。与阴性对照组和KMT2A过表达并敲低lncRNA-HOTAIR表达组相比,KMT2A过表达组以及lncRNA-HOTAIR过表达组EdU+细胞比例均明显升高(P<0.01)。与阴性对照组相比,KMT2A沉默组以及lncRNA-HOTAIR沉默组EdU+细胞比例均明显下降(P<0.01),KMT2A过表达组以及lncRNA-HOTAIR过表达组p-Akt和p-mTOR表达水平明显升高(P<0.01)。结论:KMT2A能够与lncRNA-HOTAIR相互结合,促进Akt/mTOR信号通路的活化,进而促进急性髓系白血病细胞增殖。Objective: To investigate the expression of lysine methyltransferase 2A(KMT2A) in acute myeloid leukemia(AML) cells and its molecular mechanism affecting the proliferation of AML cells. Methods: Co-immunoprecipitation assay was used to detect the binding of KMT2A to long non-coding RNA-HOX transcript antisense RNA(lncRNA-HOTAIR). A ML cell proliferation was detected by 5-ethynyl-2′-deoxyuridine(EdU) assay. Results: The PCR amplification signal of KMT2A group was significantly stronger than that of the negative control group and IgG group(P<0.01). Compared with t he negative control group and KMT2A-OE + lncRNA-HOTAIR-KD group, the ratio of EdU+ cells in both KMT2A-OE g roup and lncRNA-HOTAIR-OE group significantly increased(P<0.01). Compared with negative control group, the ratio o f EDU+ cells in KMT2A-KD group and lncRNA-HOTAIR-KD group significantly decreased(P<0.01), the expression l evels of p-Akt and p-m TOR in both KMT2A-OE group and lncRNA-HOTAIR-OE group significantly increased(P<0.01). C onclusion: KMT2A can interact with lncRNA-HOTAIR to promote the activation of Akt/mTOR signaling pathway, t hus promoting the proliferation of AML cells.

关 键 词：急性髓系白血病 赖氨酸甲基转移酶2A 长链非编码RNA-HOX转录反义RNA 增殖 Akt/mTOR信号通路 

分 类 号：R733.71[医药卫生—肿瘤]