中国实用儿科杂志

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miR-125b对儿童典型急性早幼粒细胞白血病的影响

王丽娜黄礼彬梁燕妮张晓莉柯志勇罗学群   

  1. 作者单位:中山大学附属第一医院儿科,广东 广州 510080
  • 出版日期:2014-11-06 发布日期:2014-10-29
  • 通讯作者: 罗学群 
  • 基金资助:

    广东省自然科学基金面上项目(项目编号:07001649)

MiR-125b regulates pediatric classical APL cells proliferation,apoptosis and drug resistance by targeting Bak1.

WANG Li-naHUANG Li-binLIANG Yan-niZHANG Xiao-liKE Zhi-yongLUO Xue-qun.   

  1. Department of Pediatrics, the First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080, China
  • Online:2014-11-06 Published:2014-10-29

摘要:

目的 探讨miR-125b对儿童典型急性早幼粒细胞白血病(APL)发生发展的影响及其机制,期求新的策略治疗耐药性APL。方法 用在线软件预测miR-125b的靶基因,并通过双荧光报告及蛋白印迹技术进行验证;用qRT-PCR及western blot技术检测来自中山大学附属第一医院及华南地区儿童APL协作组其他医院2007年3月至2012年9月收治的33例患者在初诊、缓解或复发时期骨髓标本中miR-125b及其靶基因的表达,进行体内证实;在细胞系水平过表达或抑制表达miR-125b,用 MTT、流式细胞技术等研究miR-125b对白血病细胞增殖、凋亡

关键词: 儿童, 典型急性早幼粒细胞白血病, miR-125b, Bak1, 耐药

Abstract:

Abstract:Objective To explore the role of miR-125b in pediatric classical APL, in order to seek new therapeutic strategies for drug resistant APL. Methods The target genes of miR-125b were predicted online, validated by Dual-luciferase assay and western blot assay. MiR-125b expression levels were measured in 33 matched-pair APL samples(treated in the First Affiliated Hospital of Sun Yat-sen University and other members of South China Children APL Cooperative Group from March 2007 to September 2012)at initial diagnosis and complete remission (CR) and in 5 relapsed patients by qRT-PCR. Proliferation and apoptosis were analyzed respectively using the RNA transfection, MTT assay and flow cytometry. Results The expression of miR-125b was up-regulated in pediatric APL at diagnosis and relapse bone marrow samples, but returned to normal after complete remission; miR-125b could promote leukemic cell proliferation and inhibit cell apoptosis by regulating the expression of tumor suppressor Bak1. Remarkably,it was also found to be up-regulated in leukemic drug-resistant cells(NB4-R1、NB4-R2及HL-60/DOX), and overexpression of exogenous miR-125b could increase their resistance to therapeutic drugs. Conclusion MiR-125b can regulate pediatric classical APL cells proliferation, apoptosis and drug resistance  by repressing BAK1 protein expression.

Key words: pediatric, classical acute promyelocytic leukemia (APL), miR-125b, Bak1, drug resistance

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