Upregulation of miR-155 induces cell cycle arrest and apoptosis in chronic myeloid leukemia

Abstract

Background and Aims: According to the increasing evidence, abnormal expression of microRNAs is associated with tumorigenesis, tumor spread, and relapse in leukemias, including chronic myeloid leukemia (CML). The present study aimed to investigate the effect of miR-155 overexpression in K562 cells on cell cycle arrest and apoptosis induction. Materials and Methods: The pLenti-III-pre miR-155-GFP vector was used to increase miR-155 expression in the K562 cell line through nucleofection compared to the pLenti-III-Backbone-GFP vector as a control group (Backbone). The flow cytometry method was employed to confirm the expression of the vector containing miR-155 in damaged cells. After transfection, the expression levels of miR-155, BAX, BCL2, CASP3, and TP53 were measured by the RT-qPCR method. The propidium iodide (PI) dye was used to study the cell cycle, and the stained cells were read by flow cytometry. The statistical significance was also defined as a P-value less than 0.05. Results: After confirming the increase in miR-155 expression when cells transfected with miR-155 were compared with cells transfected with Backbone, cell cycle arrest was observed in the miR-155 group. In the cells with increased expression of miR-155, the change in G0/S and G1/S ratios compared to Backbone was shown to be 7.5 and 4.5, respectively (P<0.05). Moreover, 48 hours after transfection and in the group expressing miR-155, the expression of TP53, BAX, and CASP3 genes increased, and the expression of BCL2 decreased (P<0.05). Conclusion: The increase in the level of miR-155 caused cell cycle arrest and increased pro-apoptotic gene expression, which indicates that miR-155 inhibits tumor growth in CML.

Keywords

• apoptosis
• bax
• bcl-2
• casp3
• cell cycle
• chronic myelogenous leukemia
• microrna-155
• tp53