Anticancer properties of vincristine is modulated by microRNAs in acute lymphoblastic leukemia Nalm6 cell line.

Abstract

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.