Myc诱导的核抗原通过调控蛋白激酶B/哺乳动物雷帕霉素靶蛋白/信号通路促进急性髓细胞性白血病细胞增殖  

Myc induced nuclear antigen promotes acute myelocytic leukemia proliferation through regulation of Akt/mTOR signaling pathway

作　　者：杭海芳[1] 路伟 俞夜花[1] 庞淯阳 王海云[2] HANG Haifang;LU Wei;YU Yehua;PANG Yuyang;WANG Haiyun(Department of Hematology,Shanghai Ninth People´s Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200011,China;Department of Emergency,Shanghai Ninth People´s Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200011,China)

机构地区：[1]上海交通大学医学院附属第九人民医院血液内科,上海200011 [2]上海交通大学医学院附属第九人民医院急诊科,上海200011

出　　处：《安徽医药》2024年第7期1339-1343,共5页Anhui Medical and Pharmaceutical Journal

基　　金：国家自然科学基金项目(81900145)。

摘　　要：目的探讨Myc诱导的核抗原(Myc induced nuclear antigen,MINA)在急性髓细胞性白血病(AML)中的表达及其对HL-60细胞的增殖影响及其分子机制。方法研究时间为2021年5月至2023年1月。AML数据集来自癌症基因组图谱(TCGA)。通过TCGA数据库下载AML的临床信息和MINA的表达水平。构建MINA基因的过表达慢病毒载体,通过慢病毒感染,建立稳定MINA基因过表达的人原髓细胞白血病细胞(HL-60)细胞系,通过细胞计数法检测其对细胞增殖的影响;蛋白质印迹法检测MINA对HL-60细胞蛋白激酶B(Akt)、哺乳动物雷帕霉素靶蛋白(mTOR)磷酸化的影响。TCGA数据库分析MINA与mTOR在AML中表达的相关性。结果分析TCGA数据库,结果显示MINA mRNA在AML中表达16.25±0.58明显高于健康对照者10.20±0.29,MINA的表达水平与AML病人预后密切相关,相对于低表达者,高表达MINA的AML癌病人预后较差(HR=2.30,P=0.003)。成功构建稳定MINA高表达的HL-60细胞系,过表达MINA促进HL-60细胞增殖,第6天细胞数过表达组明显高于对照组(P<0.01);过表达MINA可明显增加Akt和mTOR的磷酸化水平,Akt抑制剂哌立福新(Perifosine)可逆转过表达MINA导致的HL-60细胞增殖。MINA与mTOR的表达水平在AML中具有明显的正相关性(r=0.36,P<0.01)。结论MINA在AML病人中高表达,高表达MINA的AML病人预后较差,MINA可能通过调控Akt/mTOR通路促进AML细胞增殖。Objective To investigate the expression of myc induced nuclear antigen(MINA)in acute myeloid leukemia(AML)and the effects of MINA on the proliferation and its mechanism in HL-60 cells.Methods The research period was from May 2021 to January 2023.AML dataset was obtained from the Cancer Genome Atlas(TCGA).The data set of patients with AML was downloaded from TCGA,and MINA gene expression profile and clinical information were obtained.A lentiviral MINA expression vector was constructed.A stable MINA overexpressing HL-60 cell line was established through lentiviral packaging system.The effects of MINA overexpression on the proliferation of HL-60 cells were detected by cell counting.The expression of Akt and mTOR was detected by Western blotting.The relationship between MINA and mTOR was analyzed using TCGA database.Results Analysis of TCGA database showed that compared with health people(10.20±0.29),MINA mRNA was highly expressed in AML(16.25±0.58).The expression level of MINA was closely correlated with prognosis of AML patients.Results showed that higher levels of MINA were associated with a shorter overall survival(OS)time than the low-expression group(HR=2.30,P=0.003).Stable HL-60 cells with MINA overexpression were successfully constructed.Overexpression of MINA promoted HL-60 cells proliferation.On the 6th day,the number of cells was significantly higher in the overexpression group than that in the control group(P<0.01).Overexpression of MINA promoted the proliferation of HL-60 cells through activating Akt and mTOR phosphorylation.MINA overexpression induced cell proliferation was reversed by treatment with Akt inhibitor perifosine.There was a significant positive correlation between the expression of MINA and mTOR in AML(r=0.36,P<0.01).Conclusion MINA is highly expressed in AML patients,and AML patients with high MINA expression have a poor prognosis.MINA promotes the proliferation of cells through the Akt/mTOR pathway in AML.

关 键 词：白血病 髓样 急性 抗原 核 Myc诱导的核抗原 预后 增殖 蛋白激酶B/哺乳动物雷帕霉素靶蛋白 

分 类 号：R733.71[医药卫生—肿瘤]