microRNAs' differential regulations mediate the progress of Human Papillomavirus (HPV)-induced Cervical Intraepithelial Neoplasia (CIN).

microRNAs' differential regulations mediate the progress of Human Papillomavirus (HPV)-induced Cervical Intraepithelial Neoplasia (CIN).
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microRNAs 差异调节介导人乳头瘤病毒 (HPV) 诱导的宫颈上皮内瘤变 (CIN) 的进展

DOI:
10.1186/s12918-015-0145-3
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发表时间:
2015-02-07
影响因子:
--
通讯作者:
Lu H
Lu H
中科院分区:
生物2区
文献类型:
--
作者:
Mo W;Tong C;Zhang Y;Lu H

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microRNA (miRNA) 对靶标 mRNA 的直接调控受到 miRNA 之外的复杂因素的影响。因此,在癌变过程的不同阶段,miRNA可能调控不同的靶点,我们称之为“miRNA的差异调控”。 HPV 诱导的宫颈上皮内瘤变 (CIN) 是宫颈癌形成之前的重要癌前病变。目前,CIN进展的分子机制仍然知之甚少,从miRNA差异调控的角度来阐明这一点是很有趣的。在本研究中,我们对CIN进展过程中三个阶段(正常、CIN I和CIN III)的总共24个宫颈样本的miRNA和mRNA进行了转录组分析,提出了SIG++算法来检测具有显着调控变化的miRNA-mRNA对,并进一步提出了有效配对、有效靶标和相关效应生物过程的定义,作为构建miRNA差异调控网络的基本步骤。最后,针对从正常阶段进展到CIN I阶段的病程和从CIN I阶段进展到CIN III阶段的病程,分别基于两种不同的策略构建miRNA差异调控网络:一种是基于人类GO生物过程的知识,检测有效靶点和相关效应生物过程,另一种是单纯基于文献综述,检测与宫颈癌发生和发展密切相关的靶点。 对揭示促进 CIN 发展的机制具有指导意义。该研究提供了miRNA差异调控的概念、疾病发展过程中如何识别它们的算法以及如何构建具有指导性生物学意义的miRNA差异调控网络的策略。最终构建的网络为理解 CIN 进展提供了线索。本文的在线版本 (doi:10.1186/s12918-015-0145-3) 包含补充材料,可供授权用户使用。
microRNA (miRNA)’s direct regulation on target mRNA is affected by complex factors beyond miRNA. Therefore, at different stages during the course of carcinogenesis, miRNA may regulate different targets, which we termed ‘miRNA’s differential regulation’. HPV-induced cervical intraepithelial neoplasia (CIN) is an important pre-cancerous course ahead of cervical cancer formation. Currently, the molecular mechanisms of CIN progress remain poorly understood, and it is interesting to unravel this from the perspective of miRNA differential regulation. In this study, we performed transcriptome analysis of miRNAs and mRNAs for the totally 24 cervical samples in three stages (normal, CIN I, and CIN III) along CIN progress, and proposed the SIG++ algorithm to detect the miRNA — mRNA pairs with significant regulation change, and further proposed the definitions of Efficient Pair, Efficient Target, and Related Effector Biological Process, as the elemental steps to construct miRNA differential regulatory network. Finally, for the course of disease progressing from normal stage to CIN I stage, and for the course of disease progressing from CIN I stage to CIN III stage, miRNA differential regulatory networks were constructed, respectively, based on two distinct strategies: one is founded on the knowledge of human GO biological processes to detect Efficient Targets and Related Effector Biological Processes, the other is solely founded on literature review to detect the targets closely related to cervical carcinogenesis and instructive in revealing mechanisms that promote CIN development. This study provided the conception of miRNA’s differential regulation, the algorithm for how to identify them during disease development, and the strategy for how to construct miRNA differential regulatory network with instructive biological meanings. The finally constructed networks provide clues for understanding CIN progress. The online version of this article (doi:10.1186/s12918-015-0145-3) contains supplementary material, which is available to authorized users.
7 基因表达评分可预测宫颈癌的放射反应。
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