| 杭海芳,路伟,俞夜花,等.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[J].安徽医药,2024,28(7):1339-1343. |
| 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 |
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| DOI：10.3969/j.issn.1009-6469.2024.07.014 |
| 中文关键词: 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 |
| 英文关键词: Leukemia, myeloid, acute Antigens, nuclear Myc induced nuclear antigen Prognosis Proliferation Akt/mTORpatients |
| 基金项目:国家自然科学基金项目( 81900145) |
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| 中文摘要: |
| 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。 |
| 英文摘要: |
| Objective To investigate the expression of myc induced nuclear antigen (MINA) in acute myeloid leukemia (AML) andthe 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 fromTCGA, 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 showedthat 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 shorteroverall 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 HL60 cells through activating Akt and mTOR phosphorylation. MINA overexpression induced cell proliferation was reversed by treatmentwith 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. |
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