中国临床药理学杂志2024，Vol.40Issue(13)：1855-1859,5.DOI:10.13699/j.cnki.1001-6821.2024.13.002
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
摘要
Abstract
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-135a 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 100 μmol·L-1 for 24 hours,and then detected the cell viability and apoptosis rate in each group.Results The expression of MYC 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 were 1.00±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 0,0.01,1,100 μmol·L-1venaclar 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 1 μmol·L-1 venaclar drug concentration(P＜0.05).The methods showed that the apoptosis rates in miR-NC group at 0,0.01,1,100 μmol·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 between the two groups only in 1 μmol·L-1 venaclar drug concentration(P＜0.05).Conclusion The results of this study reveal that miR-135a/MYC mediates the mechanism of resistance to venaclar in the treatment of MDS and AML.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Key words
miR-135a/MYC/venaclar/myelodysplastic syndrome/acute myeloid leukemia/drug resistance mecha-nism分类
医药卫生引用本文复制引用
郭素青,石锐,吴燕,李英华..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[J].中国临床药理学杂志,2024,40(13):1855-1859,5.基金项目
2022年度河北省医学科学研究课题计划基金资助项目(20220462) （20220462）
