miRNA-mRNA correlation-network modules in human prostate cancer and the differences between primary and metastatic tumor subtypes.
miRNA-mRNA correlation-network modules in human prostate cancer and the differences between primary and metastatic tumor subtypes.
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DOI：
10.1371/journal.pone.0040130
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zhang K
中科院分区：
文献类型：
--
作者：
Zhang W;Edwards A;Fan W;Flemington EK;Zhang K
最近的研究表明mirna在癌症发病机制中的作用。前列腺癌是男性中最常见的癌症。与其他主要类型的癌症不同，在大多数前列腺肿瘤中，没有单个基因被确定为突变。这意味着基因的表达谱，包括非编码mirna，可能在这种癌症的个体病例中存在很大差异。类内变异性使得利用前列腺肿瘤样本的高维微阵列数据重建或推断疾病特异性miRNA-mRNA相关性和调节模块网络成为可能。此外，由于mirna和肿瘤抑制基因通常具有组织特异性，因此miRNA-mRNA模块可能在原发性前列腺癌（PPC）和转移性前列腺癌（MPC）之间存在差异。我们在此进行了计算机分析，以探索两种肿瘤亚型中miRNA-mRNA相关网络模块。我们的分析分别鉴定出PPC和MPC的5个miRNA-mRNA模块对（MPs）。每个MP包括一个正连接（相关）模块和一个负连接（相关）模块。每个模块的mirna或mrna（基因）数量为2 ~ 8个或6 ~ 622个。就涉及的生物学见解而言，为PPC发现的模块比为MPC发现的模块更具信息性。特别是，PPC中的一个负连接模块与公认的mirna介导的转录后调控理论非常吻合。也就是说，相关mrna（~ 620）的3'UTR序列富含7个模块化mirna的靶位基序，has-miR-106b, -191, -19b, -92a, -92b， -93和-141。大约330个GO术语和KEGG通路，包括维持组织稳态并在抑制癌细胞增殖中起关键作用的tgf - β信号通路，在模块化基因列表中被过度代表（adj.p<0.05）。这些计算鉴定的模块为mirna在前列腺癌发展中的干扰提供了显著的生物学证据，值得在独立实验室研究中进一步跟进。
Recent studies have shown the contribution of miRNAs to cancer pathogenesis. Prostate cancer is the most commonly diagnosed cancer in men. Unlike other major types of cancer, no single gene has been identified as being mutated in the majority of prostate tumors. This implies that the expression profiling of genes, including the non-coding miRNAs, may substantially vary across individual cases of this cancer. The within-class variability makes it possible to reconstruct or infer disease-specific miRNA-mRNA correlation and regulatory modular networks using high-dimensional microarray data of prostate tumor samples. Furthermore, since miRNAs and tumor suppressor genes are usually tissue specific, miRNA-mRNA modules could potentially differ between primary prostate cancer (PPC) and metastatic prostate cancer (MPC). We herein performed an in silico analysis to explore the miRNA-mRNA correlation network modules in the two tumor subtypes. Our analysis identified 5 miRNA-mRNA module pairs (MPs) for PPC and MPC, respectively. Each MP includes one positive-connection (correlation) module and one negative-connection (correlation) module. The number of miRNAs or mRNAs (genes) in each module varies from 2 to 8 or from 6 to 622. The modules discovered for PPC are more informative than those for MPC in terms of the implicated biological insights. In particular, one negative-connection module in PPC fits well with the popularly recognized miRNA-mediated post-transcriptional regulation theory. That is, the 3′UTR sequences of the involved mRNAs (∼620) are enriched with the target site motifs of the 7 modular miRNAs, has-miR-106b, -191, -19b, -92a, -92b, -93, and -141. About 330 GO terms and KEGG pathways, including TGF-beta signaling pathway that maintains tissue homeostasis and plays a crucial role in the suppression of the proliferation of cancer cells, are over-represented (adj.p<0.05) in the modular gene list. These computationally identified modules provide remarkable biological evidence for the interference of miRNAs in the development of prostate cancers and warrant additional follow-up in independent laboratory studies.
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影响因子：
50.3
作者：
Taylor BS;Schultz N;Hieronymus H;Gopalan A;Xiao Y;Carver BS;Arora VK;Kaushik P;Cerami E;Reva B;Antipin Y;Mitsiades N;Landers T;Dolgalev I;Major JE;Wilson M;Socci ND;Lash AE;Heguy A;Eastham JA;Scher HI;Reuter VE;Scardino PT;Sander C;Sawyers CL;Gerald WL
通讯作者：
Gerald WL
DOI：
10.1073/pnas.97.18.10101
发表时间：
2000-08-29
影响因子：
11.1
作者：
Alter, O;Brown, PO;Botstein, D
通讯作者：
Botstein, D
影响因子：
5.8
作者：
Joshi, Anagha;De Smet, Riet;Michoel, Tom
通讯作者：
Michoel, Tom
Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.
影响因子：
4.4
作者：
Kulp DC;Jagalur M
通讯作者：
Jagalur M