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套细胞淋巴瘤中微小RNA、基因及其调控的网络分析

Network analysis of microRNAs, genes and their regulation in mantle cell lymphoma.

作者信息

Deng Si-Yu, Guo Xiao-Xin, Wang Ning, Wang Kun-Hao, Wang Shang

机构信息

College of Computer Science and Technology, Jilin University, Changchun, China E-mail :

出版信息

Asian Pac J Cancer Prev. 2015;16(2):457-63. doi: 10.7314/apjcp.2015.16.2.457.

Abstract

The pathogenesis of mantle cell lymphoma, a special subtype of lymphoma that is invasive and indolent and has a median survival of 3 to 4 years, is still partially unexplained. Much research about genes and miRNAs has been conducted in recent years, but interactions and regulatory relations of genetic elements which may play a vital role in genesis of MCL have attracted only limited attention. The present study concentrated on regulatory relations about genes and miRNAs contributing to MCL pathogenesis. Numerous experimentally validated raw data were organized into three topology networks, comprising differentially expressed, associated and global examples. Comparison of similarities and dissimilarities of the three regulating networks, paired with the analysis of the interactions between pairs of elements in every network, revealed that the differentially expressed network illuminated the carcinogenicity mechanism of MCL and the related network further described the regulatory relations involved, including prevention, diagnosis, development and therapy. Three kinds of regulatory relations for host genes including miRNAs, miRNAs targeting genes and genes regulating miRNAs were concluded macroscopically. Regulation of the differentially expressed miRNAs was also analyzed, in terms of abnormal gene expression affecting the MCL pathogenesis. Special regulatory relations were uncovered. For example, auto-regulatory loops were found in the three topology networks, key pathways of the nodes being highlighted. The present study focused on a novel point of view revealing important influencing factors for MCL pathogenesis.

摘要

套细胞淋巴瘤是淋巴瘤的一种特殊亚型,具有侵袭性和惰性,中位生存期为3至4年,其发病机制仍部分不明。近年来,人们对基因和微小RNA(miRNA)进行了大量研究,但在套细胞淋巴瘤发生过程中可能起关键作用的遗传元件之间的相互作用和调控关系仅受到有限关注。本研究聚焦于对套细胞淋巴瘤发病机制有贡献的基因和miRNA的调控关系。大量经过实验验证的原始数据被整理成三个拓扑网络,包括差异表达、关联和全局示例。对这三个调控网络的异同进行比较,并结合对每个网络中各元件对之间相互作用的分析,结果表明差异表达网络阐明了套细胞淋巴瘤的致癌机制,而相关网络进一步描述了所涉及的调控关系,包括预防、诊断、发展和治疗。宏观上总结了宿主基因的三种调控关系,包括miRNA、靶向基因的miRNA和调控miRNA的基因。还从影响套细胞淋巴瘤发病机制的异常基因表达方面分析了差异表达miRNA的调控。发现了特殊的调控关系。例如,在三个拓扑网络中发现了自调控环,突出了节点的关键途径。本研究聚焦于一个新颖的视角,揭示了套细胞淋巴瘤发病机制的重要影响因素。

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