miR-144在β地中海贫血中的表达及作用研究  

Expression and Function of miR-144 in β-Thalassemia

作　　者：杨兰 凌玲 杨帆 杨蕾 戴志晨 郁多男 YANG Lan;LING Ling;YANG Fan;YANG Lei;DAI Zhi-Chen;YU Duo-Nan(Yangzhou University Medical College/Jiangsu Key Laboratory of Experimental&Translational Non-coding RNA Research,Yangzhou 225009,Jiangsu Province,China)

机构地区：[1]扬州大学医学院/江苏省非编码RNA基础与临床转化重点实验室,江苏扬州225009

出　　处：《中国实验血液学杂志》2025年第2期491-497,共7页Journal of Experimental Hematology

基　　金：国家自然科学基金面上项目(81470277,81870096)。

摘　　要：目的:探讨microRNA-144(miR-144)在β地中海贫血(β-thal)中的表达及作用。方法:通过实时荧光定量PCR(qRT-PCR)法分析miR-144在小鼠红白血病(MEL)细胞和小鼠胚胎肝来源的红系前体细胞分化过程中的表达情况;qRT-PCR法检测野生型(WT)小鼠和β-thal小鼠外周血和14.5 d胚胎肝细胞中miR-144的表达水平以及β地中海贫血患者外周血中miR-144的表达水平;流式细胞术分析轻度和重度β-thal小鼠外周血中Ter119和CD71双阳性细胞的比例变化,并对比轻度和重度β-thal小鼠和患者外周血中miR-144的表达水平;分选得到WT小鼠和β-thal小鼠的骨髓有核红细胞,通过基因芯片分析miR-144潜在靶基因的表达水平。结果:在小鼠MEL细胞和胚胎肝细胞向红系定向分化过程中,miR-144的表达水平逐步升高(r_(MEL)=0.97,r_(胚胎肝)=0.86);与WT小鼠相比,β-thal小鼠外周血以及14.5 d胚胎肝细胞中miR-144表达水平明显升高(P<0.05);与健康对照组相比,β地中海贫血患者外周血中miR-144表达水平明显升高(P<0.05);重度β-thal小鼠和人外周血中miR-144的表达水平较轻度β-thal小鼠和人均明显升高(P<0.05);β-thal小鼠有核红细胞中miR-144的潜在靶基因相较于WT组表达水平明显下降。结论:miR-144在红系发育过程中逐渐升高,且相较于轻度β-thal,重度β-thal外周血中miR-144的表达水平更高,miR-144有望成为临床β-thal的辅助诊断指标。Objective:To explore the expression and function of microRNA-144(miR-144)inβ-thalassemia(β-thal).Methods:The expression of miR-144 during the differentiation of murine erythroleukemia(MEL)cells and mouse embryonic liver-derived erythroid precursor cells was analyzed by real-time fluorescence quantitative PCR(qRT-PCR);The expression levels of miR-144 in peripheral blood and day-14.5 embryonic hepatocytes of wild-type(WT)andβ-thal mice,as well as the expression levels of miR-144 in peripheral blood ofβ-thal patients,was also measured by qRT-PCR.The proportion of Ter119 and CD71 double positive cells in peripheral blood of mild and severeβ-thal mice was analyzed by flow cytometry,and the expression levels of miR-144 in the peripheral blood of mild and severeβ-thal mice and patients were compared;Bone marrow nucleated erythrocytes from WT mice andβ-thal mice were sorted and the expression levels of miR-144 potential target genes were analyzed by gene chip.Results:The expression levels of miR-144 were gradually increased during the directed differentiation of mouse MEL cells and embryonic hepatocytes to the erythroid lineage(r_(MEL)=0.97,r_(embryonic hepatocytes)=0.86);Compared with WT mice,the expression levels of miR-144 in peripheral blood and 14.5-day embryonic hepatocytes ofβ-thal mice were significantly increased(P<0.05);Compared with healthy controls,the patients withβ-thal showed an increased expression levels of miR-144 in peripheral blood(P<0.05).Compared with mice and humans with mildβ-thal,the expression levels of miR-144 in peripheral blood of those with severeβ-thal were significantly increased(P<0.05).The expressions of potential target genes of miR-144 in nucleated erythroid cells of theβ-thal mice were significantly reduced compared to the WT group.Conclusion:The expression level of miR-144 gradually increases in erythroid development,and compared with mildβ-thal patients,the expression level of miR-144 in the peripheral blood is higher in severeβ-thal patients.MiR-144 is expected to be

关 键 词：miR-144 红系分化 Β地中海贫血 

分 类 号：R556.61[医药卫生—血液循环系统疾病]