Sen Kamalika, Sarkar Arijita, Maji Ranjan Kumar, Ghosh Zhumur, Gupta Sanjib, Ghosh Tapash Chandra
Bioinformatics Centre, Bose Institute, P 1/12, C.I.T. Scheme VII M, Kolkata-700 054, India.
Mol Biosyst. 2016 Nov 15;12(12):3633-3642. doi: 10.1039/c6mb00568c.
Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by increased proliferation or abnormal accumulation of granulocytic cell line without the depletion of their capacity to differentiate. A reciprocal chromosomal translocation proceeding to the 'Philadelphia chromosome', involving the ABL proto-oncogene and BCR gene residing on Chromosome 9 and 22 respectively, is observed to be attributed to CML pathogenesis. Recent studies have been unraveling the crucial role of genomic 'dark matter' or the non-coding repertoire in cancer initiation and progression. The intricate cross-talk between competitive endogenous RNAs (ceRNAs) provides a scaffold to systematically functionalize the miRNA response element harboring non-coding RNAs and incorporate them with the protein-coding RNA dimension in complex ceRNA networks. This network of coding and non-coding transcriptome linked by shared miRNAs evidently offers a platform to elucidate the complex regulatory interactions at the post-transcriptional level in human cancers. In this context, analyzing CML, from the perspective of the ceRNA hypothesis, surely craves intensive attention and a comprehensive discussion. Here, we performed RNA-seq data analysis to retrieve Lymphoblastoid and CML coding as well as non-coding repertoire and constructed a ceRNA network for the CML cell line, considering the non-cancer lymphoblastoid cell line as the control. We investigated if any alteration exists in the ceRNA landscape of the transcripts which are exhibiting differential expression across the two cell lines and observed that the major ceRNA regulators vary in cancer network when compared with the Lymphoblastoid network. The top ranked significant functional modules in the ceRNA network display cancer associated attributes and reveal putative regulators in CML pathogenesis.
慢性粒细胞白血病（CML）是一种骨髓增殖性疾病，其特征在于粒细胞系的增殖增加或异常积聚，而其分化能力并未耗尽。人们观察到，一种导致“费城染色体”形成的相互染色体易位，涉及分别位于9号和22号染色体上的ABL原癌基因和BCR基因，这被认为是CML发病机制的原因。最近的研究一直在揭示基因组“暗物质”或非编码序列在癌症发生和发展中的关键作用。竞争性内源RNA（ceRNA）之间复杂的相互作用提供了一个框架，可系统地使含有非编码RNA的miRNA反应元件功能化，并将它们纳入复杂ceRNA网络中的蛋白质编码RNA维度。这个由共享miRNA连接的编码和非编码转录组网络显然提供了一个平台，以阐明人类癌症转录后水平上复杂的调控相互作用。在这种背景下，从ceRNA假说的角度分析CML，无疑需要深入关注和全面讨论。在这里，我们进行了RNA测序数据分析，以检索淋巴母细胞和CML的编码以及非编码序列，并以非癌性淋巴母细胞系作为对照，构建了CML细胞系的ceRNA网络。我们研究了在这两种细胞系中表现出差异表达的转录本的ceRNA格局是否存在任何改变，并观察到与淋巴母细胞网络相比，癌症网络中的主要ceRNA调节因子有所不同。ceRNA网络中排名靠前的重要功能模块显示出与癌症相关的属性，并揭示了CML发病机制中的假定调节因子。
