miR-135a/MYC介导维奈克拉治疗骨髓增生异常综合征与急性髓系白血病的耐药机制研究  

Mechanism of miR-135a/MYC-mediated resistance to venaclar in the treatment of myelodysplastic syndrome and acute myeloid leukemia

作　　者：郭素青 石锐 吴燕 李英华 GUO Su-qing;SHI Rui;WU Yan;LI Ying-hua(Department of Hematology,Hengshui People's Hospital,Hengshui 053000,Hebei Province,China)

机构地区：[1]衡水市人民医院血液内科,河北衡水053000

出　　处：《中国临床药理学杂志》2024年第13期1855-1859,共5页The Chinese Journal of Clinical Pharmacology

基　　金：2022年度河北省医学科学研究课题计划基金资助项目(20220462)。

摘　　要：目的探讨miR-135a/MYC介导维奈克拉治疗骨髓增生异常综合征(MDS)与急性髓系白血病(AML)的耐药机制。方法选取病例86例,其中健康供者23例(对照组),MDS维奈克拉耐药患者47例(MDS组),由骨髓增生异常综合征转化的AML维奈克拉耐药患者16例(AML组),检测3组miR-135a和MYC的表达水平。将THP1细胞分为miR-NC组(转染无义序列)和miR-135a minics组(转染miR-135a minics),用含0、0.01、1、100μmol·L^(-1)的维奈克拉处理细胞24 h,检测各组细胞活力和凋亡率。结果对照组、MDS组和AML组患者miR-135a的表达水平分别为1.00±0.14、0.21±0.04和0.25±0.08,MYC的蛋白表达水平分别为1.00±0.15、1.31±0.12和1.49±0.16(P<0.05)。在细胞水平方面,BMSCs组、MUTZ-1组、THP1组MYC mRNA表达水平分别为1.00±0.11、1.31±0.15和1.93±0.23,MYC蛋白表达水平分别为1.00±0.15、1.57±0.22和1.97±0.31,在统计学上差异均有统计学意义(均P<0.05)。细胞活力检测结果显示,在0、0.01、1、100μmol·L^(-1)维奈克拉药物浓度下,miR-NC组细胞活力分别为(100.00±13.26)%、(92.33±10.28)%、(85.41±11.37)%和(28.24±6.02)%,miR-135a mimics组细胞活力分别为(105.12±12.35)%、(82.11±12.07)%、(46.13±8.06)%和(18.20±5.03)%,仅在1μmol·L^(-1)维奈克拉药物浓度中2组在统计学上差异有统计学意义(P<0.05)。细胞凋亡检测结果显示:在0、0.01、1、100μmol·L^(-1)维奈克拉药物浓度下,miR-NC组凋亡率分别为(100.00±11.45)%、(92.48±12.04)%、(108.72±9.63)%和(207.15±21.49)%,miR-135a mimics组的细胞凋亡率分别为(106.34±16.21)%、(117.26±10.13)%、(269.41±23.59)%和(184.33±19.28)%,仅在1μmol·L^(-1)维奈克拉药物浓度中2组差异在统计学上有统计学意义(P<0.05)。结论miR-135a/MYC介导维奈克拉治疗MDS和AML的耐药机制。Objective To investigate the mechanism of miR-135a/MYC-mediated resistance to venaclar treatment in myelodysplastic syndromes(MDS)with acute myeloid leukaemia(AML).Methods Eighty-six cases of patients were selected,including 23 healthy donors(control group),47 MDS patients with vinecella resistance(MDS group),and 16 AML patients with vinecella resistance transformed from myelodysplastic syndrome(AML group).The expression levels of miR-135 a and MYC in the tissues of the three groups were detected.THP1 cells were divided into miR-NC group(transfected with nonsense sequence)and miR-135a minics group(transfected with miR-135a minics),and the cells were treated with venaclar concentration of 0,0.01,1,and 100μmol·L^(-1)for 24 hours,and then detected the cell viability and apoptosis rate in each group.Results The expression of MWC mRNA were 1.00±0.14,0.21±0.04,and 0.25±0.08 in patients of the NC,MDS,and AML groups,respectively;the protein expression of MYC were1.00±0.15,1.31±0.12 and 1.49±0.16,respectively(P<0.05).At the cellular level,miR-135a expression were 1.00±0.11,1.31±0.15 and 1.93±0.23 in the BMSCs,MUTZ-1 and THP1 groups;MYC protein expression were 1.00±0.15,1.57±0.22 and 1.97±0.31,the differences were significant(P<0.05).The methods showed the cell viability of miR-NC group were(100.00±13.26)%,(92.33±10.28)%,(85.41±11.37)%and(28.24±6.02)%at 0,0.01,1,100μmol·L^(-1)venaclar drug concentration,respectively;cell viability of miR-135a mimics group were(105.12±12.35)%,(82.11±12.07)%,(46.13±8.06)%and(18.20±5.03)%,respectively,there was statistical difference between the two groups only in the 1μmol·L^(-1)venaclar drug concentration(P<0.05).The methods showed that the apoptosis rates in miR-NC group at 0,0.01,1,100μmol·L^(-1)venaclar drug concentration were(100.00±11.45)%,(92.48±12.04)%,(108.72±9.63)%and(207.15±21.49)%,the apoptosis rates in miR-135a mimics group were(106.34±16.21)%,(117.26±10.13)%,(269.41±23.59)%and(184.33±19.28)%,respectively;there was statistical difference betwe

关 键 词：miR-135a/MYC 维奈克拉 骨髓增生异常综合征 急性髓系白血病 耐药机制 

分 类 号：R97[医药卫生—药品]