Integrated analysis of gene expression and microRNA regulation in three leukemia-related lymphoblastic cell lines.

Abstract RNA-sequencing technology is progressively being applied in various fields since high-throughput data analysis provides deeper mining on both the genomic and transcriptomic level. Lymphoblastic leukemogenesis is a complex process caused by abnormalities occurring during lymphocyte differentiation, and can be initiated by various triggers. Each leukemia subtype has distinct characteristics that can be identified in the corresponding cell lines; the detection of the exclusive genetic signatures of these varying cell lines is critical. Our analysis revealed that approximately 8000 human genes were differentially expressed between samples. Signaling pathways such as the NOD-like signaling pathway, cell surface receptor signaling pathways, and leukemia-related pathways were significantly regulated, as determined by KEGG annotation. Furthermore, several oncogenes and differentiation-related genes were differentially expressed between leukemia cell lines and lymphocyte types, respectively. Our miRNA analysis demonstrated that the expression of approximately one-third of all expressed miRNAs appeared to be significantly different between the leukemia cell lines studied. We also analyzed the mRNA–miRNA regulatory networks of both lymphocyte differentiation and leukemogenesis to determine key regulators of interest. We combined the results of the mRNA and miRNA analyses in order to investigate the regulatory relationship between them. This study not only identifies differences in the pathways and networks of acute lymphocytic leukemia (ALL) relative to normal lymphocytes, but also identifies unique functional characteristics of lymphoid cells and distinct gene expression patterns during lymphoid development. The discovery of leukemia-related miRNAs may provide meaningful insights into the biology of the disease.