摘要
目的探讨环状RNA SFMBT2(circ-SFMBT2)通过海绵吸附调控miR-491-5p靶向HOXA9在急性髓系白血病(AML)中的作用机制。方法选取2024年1月至9月于齐齐哈尔医学院附属第二医院血液内科就诊的AML患者(n=30)及年龄、性别匹配的良性贫血患者(对照组,n=30)为研究对象。通过实时荧光定量PCR(RT-qPCR)检测骨髓细胞中circ-SFMBT2、miR-491-5p及HOXA9的表达水平;采用细胞转染技术沉默circ-SFMBT2(si-circ-SFMBT2组),并联合转染miR-491-5p抑制剂(si-circ-SFMBT2+miR-491-5p抑制剂组),分析其对AML细胞增殖、凋亡、迁移及侵袭能力的影响。结果AML组骨髓中circ-SFMBT2和HOXA9表达水平显著高于对照组(P<0.001),miR-491-5p表达水平显著低于对照组(P<0.001)。相关性分析显示,circ-SFMBT2与miR-491-5p表达呈显著负相关(r=-0.956,P<0.001),HOXA9与miR-491-5p表达呈显著负相关(r=-0.977,P<0.001),而HOXA9与circ-SFMBT2表达呈显著正相关(r=0.977,P<0.001)。功能实验显示,与对照siRNA组相比,si-circ-SFMBT2组circ-SFMBT2及HOXA9 mRNA表达显著下调(P<0.05),miR-491-5p表达显著上调(P<0.05),AML细胞存活能力、迁移及侵袭数显著降低(P<0.05),凋亡率显著升高(P<0.05);与si-circ-SFMBT2组相比,si-circ-SFMBT2+miR-491-5p抑制剂组HOXA9 mRNA水平显著回升(P<0.05),miR-491-5p表达显著下调(P<0.05),AML细胞存活能力、迁移及侵袭数显著升高(P<0.05),凋亡率显著降低(P<0.05)。结论circ-SFMBT2在AML中呈高表达,可能通过海绵吸附作用抑制miR-491-5p表达,解除其对HOXA9的靶向抑制,进而促进AML细胞增殖、迁移及侵袭能力。
Objective To investigate the mechanistic role of circular RNA SFMBT2(circ-SFMBT2)in acute myeloid leukemia(AML)by sponging miR-491-5p and targeting HOXA9.Methods A total of 30 AML patients and 30 age-and sex-matched patients with benign anemia(control group)who visited the Department of Hematology of the Second Affiliated Hospital of Qiqihar Medical University from January to September 2024 were selected as the subjects of the study.Expression levels of circ-SFMBT2,miR-491-5p,and HOXA9 in bone marrow cells were detected by reverse transcription-quantitative PCR(RT-qPCR).Cell transfection techniques were employed to silence circ-SFMBT2(si-circ-SFMBT2 group)and co-transfect with miR-491-5p inhibitor(si-circ-SFMBT2+miR-491-5p inhibitor group).And then,the effects of these treatments on the proliferation,apoptosis,migration,and invasion capacities of AML cells were analyzed.Results The expression levels of circ-SFMBT2 and HOXA9 in the bone marrow of the AML group were significantly higher than those in the control group(P<0.001),while miR-491-5p expression was significantly lower than that in the control group(P<0.001).Correlation analysis revealed a significant negative correlation between circ-SFMBT2 and miR-491-5p expressions(r=-0.956,P<0.001),a significant negative correlation between HOXA9 and miR-491-5p expressions(r=-0.977,P<0.001),and a significant positive correlation between HOXA9 and circ-SFMBT2 expressions(r=0.977,P<0.001).Functional experiments showed that compared with the control siRNA group,the si-circ-SFMBT2 group exhibited significantly downregulated circ-SFMBT2 and HOXA9 mRNA expressions(P<0.05),upregulated miR-491-5p expression(P<0.05),reduced AML cell survival capacity,migration,and invasion counts(P<0.05),and increased apoptosis rate(P<0.05).In comparison with the si-circ-SFMBT2 group,the si-circ-SFMBT2+miR-491-5p inhibitor group showed significantly upregulated HOXA9 mRNA levels(P<0.05),downregulated miR-491-5p expression(P<0.05),increased AML cell survival capacity,migration,and invasion counts(P<0.05),and decreased apoptosis rate(P<0.05).Conclusion circ-SFMBT2 is highly expressed in AML and may act as a molecular sponge to inhibit the expression of miR-491-5p,thereby relieving its targeting inhibition of HOXA9,and then may subsequently promote the proliferation,migration,and invasive capacity of AML cells.
作者
周畅
李佳欣
尹畅
姜丽波
卢停
许玲玲
ZHOU Chang;LI Jiaxin;YIN Chang;JIANG Libo;LU Ting;XU Lingling(Department of Hematology,the Second Affiliated Hospital of Qiqihar Medical University,Qiqihar 161006,Heilongjiang,China)
出处
《右江医学》
2025年第8期681-686,共6页
Chinese Youjiang Medical Journal
基金
齐齐哈尔市科学技术局联合引导项目(LSFGG-2024038)。
