Precursor B-cell acute lymphoblastic leukemia (B-ALL), a highly diverse disease, is the most widespread pediatric malignancy characterized by cytogenetic and molecular abnormalities such as altered microRNA (miR) expression signatures. MiRs are a class of short noncoding RNAs. Dysregulation in the expression of miRs plays a crucial role in different types of cancers. Vincristine is an antineoplastic drug with a broad spectrum of activity against different hematologic malignancies and is the first-line treatment for B-ALL. Previous studies have proposed miR-17 and miR-181/b as oncomirs and miR-34/a as a tumor suppressor in Nalm6 cells, thus in the current study, we investigated the effects of vincristine treatment on the expression of miR-17, miR-34/a and miR-181/b expression levels. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay was conducted to estimate the optimal concentration of vincristine in the Nalm-6 cell line. Expression of miRs was calculated using real-time PCR. Our results showed significant downregulation of miR-17 (FC = 0.226; P < 0.0004) in Nalm6 cells after vincristine treatment. Conversely, miR-34/a (FC = 4.823; P < 0.0001) was significantly upregulated. Also, the expression of miR-181/b (FC = 0.156; P < 0.3465) was not significantly different between the vincristine treated group and the control group. In conclusion, it is proposed that one of the mechanisms by which vincristine improves B-ALL is by modulating the expression of specific miRs. These specific miRs will serve as good diagnostic and prognostic biomarkers.

中文翻译：

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在急性淋巴细胞白血病 Nalm6 细胞系中，长春新碱的抗癌特性受到 microRNA 的调节。

前体 B 细胞急性淋巴细胞白血病 (B-ALL) 是一种高度多样化的疾病，是最常见的儿科恶性肿瘤，其特征是细胞遗传学和分子异常，例如 microRNA (miR) 表达特征改变。MiR 是一类短非编码 RNA。miR 表达失调在不同类型的癌症中起着至关重要的作用。长春新碱是一种抗肿瘤药物，对不同的血液恶性肿瘤具有广谱活性，是 B-ALL 的一线治疗药物。先前的研究已提出Nalm6细胞中miR-17和miR-181/b作为癌瘤，miR-34/a作为肿瘤抑制因子，因此在本研究中，我们研究了长春新碱治疗对miR-17表达的影响， miR-34/a 和 miR-181/b 表达水平。进行3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-四唑溴化物测定以估计Nalm-6细胞系中长春新碱的最佳浓度。使用实时 PCR 计算 miR 的表达。我们的结果显示，长春新碱处理后 Nalm6 细胞中 miR-17 显着下调（FC = 0.226；P < 0.0004）。相反，miR-34/a（FC = 4.823；P < 0.0001）显着上调。此外，长春新碱治疗组和对照组之间 miR-181/b 的表达（FC = 0.156；P < 0.3465）没有显着差异。总之，长春新碱改善 B-ALL 的机制之一是通过调节特定 miR 的表达。这些特定的 miR 将作为良好的诊断和预后生物标志物。