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首页> 外文期刊>Journal of cellular biochemistry. >MicroRNA‐326 and microRNA‐200c: Two novel biomarkers for diagnosis and prognosis of pediatric acute lymphoblastic leukemia
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MicroRNA‐326 and microRNA‐200c: Two novel biomarkers for diagnosis and prognosis of pediatric acute lymphoblastic leukemia

机译：MicroRNA-326和MicroRNA-200C：两种新型生物标志物，用于儿科急性淋巴细胞白血病诊断和预后

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Abstract Multidrug resistance (MDR) is considered as the major obstacle for treating pediatric acute lymphoblastic leukemia (ALL). MicroRNAs (miRNAs) are small non coding RNAs which may potentially regulate response to chemotherapy. In this study, total RNA was isolated from bone marrow samples of 46 children with de novo ALL and 16 controls. Quantitative reverse transcriptase polymerase chain reaction was used to investigate the expression profile of the predicted miRNAs; miR‐326 and miR‐200c, and their predicted targets ABCA2, and ABCA3 transporters. The presence of minimal residual disease was studied using PCR‐SSCP (single‐strand conformation polymorphism) 1 year after treatment. The association between the miRNA expression and drug resistance was analyzed statistically. Results showed a significant down‐regulation of both miR‐326 and miR‐200c expressions in ALL patients compared with non‐cancer controls ( P ?=?0.0002, AUC?=?0.813 and P ?=?0.035, AUC?=?0.79, respectively). A considerable negative association between miR‐326 expression and MDR was identified which could raise the risk of chemoresistance by 4.8‐ fold. The expression profiles of miR‐326 and ABCA2 transporter were inversely correlated. Data revealed, a novel diagnostic role for miR‐326 and miR‐200c as potential biomarkers of pediatric ALL. Down‐regulation of miR‐326 was introduced, for the first time, as a prognostic factor for drug resistance in childhood ALL. To the best of our knowledge, this is the first time that ABCA2 transporter is proposed as a target gene for miR‐326, through which it can exert its impact on drug resistance. These data may provide novel approaches to new therapeutics and diagnostics.
机译：摘要多药耐药性（MDR）被认为是治疗小儿急性淋巴细胞白血病（全部）的主要障碍。 MicroRNA（miRNA）是小的非编码RNA，其可能会调节对化疗的反应。在这项研究中，从46名儿童的骨髓样品中分离出总RNA，De Novo全部和16个对照。定量逆转录酶聚合酶链反应研究预测的miRNA的表达谱; miR-326和miR-200c，及其预测的目标abca2和abca3运输器。使用PCR-SSCP（单链构象多态性）在治疗后进行最小残留疾病的存在。分析了miRNA表达和耐药之间的关联。结果表明，与非癌症对照相比，所有患者的MIR-326和MIR-200C表达的显着下调（P？= 0.0002，AUC？= 0.813和P？=？0.79 ， 分别）。鉴定了miR-326表达和MDR之间的相当负关联，其可以将化学抑制风险提高4.8倍。 miR-326和ABCA2转运蛋白的表达谱反向相关。数据显示，miR-326和miR-200c的新诊断作用作为儿科所有的潜在生物标志物。首次引入miR-326的下调作为儿童耐药性的预后因素。据我们所知，这是第一次提出ABCA2转运蛋白作为MIR-326的靶基因，通过它可以发挥其对耐药性的影响。这些数据可以为新治疗和诊断提供新的方法。

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