lncRNA SNHG12通过miR-409-3p/TWIST1轴调节急性髓系白血病细胞的增殖、迁移和侵袭  

IncRNA SNHG12 regulates the proliferation,migration and invasion of acute myeloid leukemia cells through the miR-409-3p/TWIST1 axis

作　　者：赵海歌 王静[2] 肖梦瑶 崔雯萱 ZHAO Haige;WANG Jing;XIAO Mengyao;CUI Wenxuan(Department of Clinical Laboratory,Affiliated Hospital of Hebei University,Baoding 071000,Hebei,China;Department of Hematology,Affiliated Hospital of Hebei University,Baoding 071000,Hebei,China)

机构地区：[1]河北大学附属医院检验科,保定071000 [2]河北大学附属医院血液内科,保定071000

出　　处：《医学研究与战创伤救治》2025年第2期135-142,共8页Journal of Medical Research & Combat Trauma Care

基　　金：保定市科技计划项目(2341ZF160)。

摘　　要：目的探讨lncRNA SNHG12是否可通过miR-409-3p/TWIST1轴调节急性髓系白血病(AML)细胞的增殖、迁移和侵袭。方法用q RT-PCR检测47例急性髓系白血病患者和47例非血液系统肿瘤性疾病患者骨髓单个核细胞中SNHG12、miR-409-3p和TWIST1 mRNA的表达水平;然后将HL-60细胞分为对照组、sh-NC组、sh-SNHG12组、sh-SNHG12+inhibitor NC组、sh-SNHG12+miR-409-3p inhibitor组、sh-SNHG12+oe-NC组、sh-SNHG12+oe-TWIST1组;用q RT-PCR检测各组细胞SNHG12、miR-409-3p和TWIST1 mRNA表达水平;CCK-8检测细胞增殖;Transwell实验检测细胞迁移和侵袭;流式细胞术检测细胞凋亡;Western blot检测细胞中TWIST1、CyclinD1、Ki67、Cleaved-caspase-3、MMP-9蛋白表达量。双荧光素酶报告基因实验检测miR-409-3p与SNHG12和TWIST1的靶向关系。结果AML患者骨髓单个核细胞和建株AML细胞中SNHG12和TWIST1 mRNA表达显著升高,miR-409-3p表达显著降低(P<0.05);下调SNHG12表达显著降低HL-60细胞中SNHG12和TWIST1 mRNA表达、A_(450)(24、48 h)值、细胞迁移和侵袭个数、TWIST1、CyclinD1、Ki67、MMP-9蛋白表达,提高凋亡率、miR-409-3p和Cleaved-caspase-3蛋白表达(P<0.05);下调miR-409-3p表达或上调TWIST1表达均可减弱下调SNHG12对HL-60细胞的抑制作用(P<0.05)。结论干扰SNHG12表达可提高miR-409-3p表达抑制TWIST1,进而抑制AML细胞增殖、迁移和侵袭。Objective This study aims to investigate whether lncRNA SNHG12 can regulate the proliferation,migration,and invasion of acute myeloid leukemia(AML)cells through the miR-409-3p/TWIST1 axis.Methods QRT-PCR was applied to detect the expression levels of SNHG12,miR-409-3p,and TWIST1 mRNA in bone marrow mononuclear cells of 47 patients with acute myeloid leukemia and 47 patients with non hematological malignancies.HL-60 cells were divided into control group,sh-NC group,sh-SNHG12 group,sh-SNHG12+inhibitor NC group,sh-SNHG12+miR-409-3p inhibitor group,sh-SNHG12+oe NC group,and sh-SNHG12+oe TWIST1 group;qRT-PCR was applied to detect the expression levels of SNHG12,miR-409-3p,and TWIST1 mRNA of cells in each group.CCK-8 was applied to detect cell proliferation;Transwell experiment was applied to detect cell migration and invasion;flow cytometry was applied to detect cell apoptosis;Western blot was applied to detect the expression levels of TWIST1,CyclinD1,Ki67,Cleaved-caspase-3,and MMP-9 proteins in cells.Dual luciferase reporter gene experiment was applied to detect the targeted relationship between miR-409-3p and SNHG12 and TWIST1.Results The expression of SNHG12 and TWIST1 mRNA was significantly increased in bone marrow mononuclear cells of AML patients and AML cell strains,the expression of miR-409-3p was signifi-cantly reduced(P<0.05).Down-regulation of SNHG12 expression significantly reduced SNHG12 and TWIST1 mRNA expression,A_(450)(24,48 hours)value,numbers of cell migration and invasion,the expression of TWIST1,CyclinD1,Ki67,MMP-9 proteins,but in-creased apoptosis rate,the expression of miR-409-3p,and Cleaved-caspase-3 proteins in HL-60 cells(P<0.05).Both down-regula-tion of miR-409-3p expression or up-regulation of TWIST1 expression were able to weaken the inhibitory effect of SNHG12 on HL-60 cells(P<0.05).Conclusion Interference in SNHG12 expression can increase miR-409-3p expression and inhibit TWIST1,there-by inhibiting proliferation,migration,and invasion of AML cells.

关 键 词：lncRNA SNHG12 miR-409-3p/TWIST1轴 急性髓系白血病 细胞 

分 类 号：R552[医药卫生—血液循环系统疾病]