Hu Yang, Xiong Qian, Yang Yadong, Wang Hai, Shu Chang, Xu Wei, Fang Xiangdong, Hu Songnian
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1-104 Beichen West Road, Chaoyang, Beijing 100101, China.
Gene. 2015 Jun 10;564(1):39-52. doi: 10.1016/j.gene.2015.03.039. Epub 2015 Mar 19.
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.
由于高通量数据分析能在基因组和转录组水平上进行更深入的挖掘，RNA测序技术正逐渐应用于各个领域。淋巴细胞白血病的发生是一个复杂的过程，由淋巴细胞分化过程中出现的异常引起，并且可以由各种触发因素引发。每种白血病亚型都有其独特的特征，可在相应的细胞系中识别；检测这些不同细胞系的独特基因特征至关重要。我们的分析表明，样本之间约有8000个人类基因存在差异表达。通过KEGG注释确定，NOD样信号通路、细胞表面受体信号通路和白血病相关通路等信号通路受到显著调控。此外，几种癌基因和分化相关基因在白血病细胞系和淋巴细胞类型之间分别存在差异表达。我们的miRNA分析表明，在所研究的白血病细胞系中，所有表达的miRNA中约有三分之一的表达似乎存在显著差异。我们还分析了淋巴细胞分化和白血病发生的mRNA-miRNA调控网络，以确定感兴趣的关键调节因子。我们结合了mRNA和miRNA分析的结果，以研究它们之间的调控关系。这项研究不仅确定了急性淋巴细胞白血病（ALL）相对于正常淋巴细胞在信号通路和网络方面的差异，还确定了淋巴样细胞的独特功能特征以及淋巴样发育过程中不同的基因表达模式。白血病相关miRNA的发现可能为该疾病的生物学研究提供有意义的见解。
