Comparison of microRNA expression profiles in K562-cells-derived microvesicles and parental cells, and analysis of their roles in leukemia.

Abstract

Microvesicles (MVs) are 30-1,000-nm extracellular vesicles that are released from a multitude of cell types and perform diverse cellular functions, including intercellular communication, antigen presentation, and transfer of proteins, messenger RNA and microRNA (also known as miR). MicroRNAs have been demonstrated to be aberrantly expressed in leukemia, and the overall microRNA expression profile may differentiate normal blood cells vs. leukemia cells. MVs containing microRNAs may enable intercellular cross-talk in vivo. This prompted us to investigate specific variations of microRNA expression patterns in MVs derived from leukemia cells. The present study examined the microRNA expression profile of MVs from chronic myeloid leukemia K562 cells and that of MVs from normal human volunteers' peripheral blood cells. The potential targets of the differentially expressed microRNAs were predicted using computational searches. Bioinformatic analyses of the predicted target genes were performed for further evaluation. The present study analyzed microRNAs of MVs derived from leukemia and normal cells, and characterized specific microRNAs expression. The results revealed that MVs derived from K562 cells expressed 181 microRNAs of the 888 microRNAs assessed. Further analysis revealed that 16 microRNAs were downregulated, while 7 were upregulated in these MVs. In addition, significant differences in microRNA expression profiles between MVs derived from K562 cells and K562 cells were identified. The present results revealed that 77 and 122 microRNAs were only expressed in MVs derived from K562 cells and in K562 cells, respectively. There were 104 microRNAs co-expressed in MVs derived from K562 cells and in K562 cells. Target gene-related pathway analyses demonstrated that the majority of the dysregulated microRNAs were involved in pathways associated with leukemia, particularly the mitogen-activated protein kinase (MAPK) and the p53 signaling pathways. By further conducting microRNA gene network analysis, the present study revealed that the miR-15a/b, miR-16, miR-17 and miR-30 families were likely to play a role in the regulation of the MAPK signaling pathway. Since K562 cells presented the t(9;22) translocation, the current study further examined the predicted function of 12 microRNAs located in chromosomes 9 [Homo sapiens (hsa)-let-7a, hsa-let-7f, miR-126, miR-126*, miR-23b, miR-24, miR-27b and miR-7] and 22 (hsa-let-7b, miR-1249, miR-130b and miR-185), which were expressed both in MVs derived from K562 cells and in K562 cells. The present study identified microRNAs of MVs from leukemia and normal cells, and characterized the expression of specific microRNAs. The current study is also the first to identify and characterize distinct microRNA expression between MVs derived from K562 cells and K562 cells. These findings highlight that a number of microRNAs from leukemia-derived MVs may contribute to the development of hematopoietic malignancies. Further investigation may reveal the function of these differentially expressed microRNAs and may provide potential targets for novel therapeutic strategies.