Principles of microRNA regulation of a human cellular signaling network

Cui, Qinghua; Yu, Zhenbao; Purisima, Enrico O.; Wang, Edwin

doi:10.1038/msb4100089

Cited by 334 publications

(303 citation statements)

References 24 publications

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“…At last, through the pathway enrichment analysis, most of the common target genes of cilque0 including c-myc, FGF5 and TGFBR1, were found to be enriched in MAPK signaling pathway. The results were consistent with the previous studies that miRNAs are trend to be enriched in signal transduction pathway (Cui et al, 2006). Interestingly, we also found these target genes were also found to be enriched in pathways in cancer.…”

Section: Pathway Enrichment Analysissupporting

confidence: 93%

“…The enrichment analysis demonstrated that most of the target genes were enriched in MAPK signaling pathways. It is expected, because most of the miRNAs involve in signal transduction pathway (Cui et al, 2006). The MAPK pathway is constituted by a serial of proteins, which transduce signal from the receptor on cell surface to DNA in the nucleus.…”

Section: Discussionmentioning

confidence: 99%

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MiRNA Synergistic Network Construction and Enrichment Analysis for Common Target Genes in Small-cell Lung Cancer

Zhang¹,

Cheng²,

Shi³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Section: Pathway Enrichment Analysissupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

MiRNA Synergistic Network Construction and Enrichment Analysis for Common Target Genes in Small-cell Lung Cancer

Zhang¹,

Cheng²,

Shi³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…signaling pathway. 20,21 Indeed, miR145 is no exception, as it targets IRS-1 (but not IRS-2), the IGF-IR and S6K (the last one, unpublished data from our laboratory). However, IRS-1 is the crucial target.…”

Section: Discussionmentioning

confidence: 99%

Growth inhibition by microRNAs that target the insulin receptor substrate-1

Rocca

Shi²,

Badin³

et al. 2009

Cell Cycle

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We have examined several microRNAs (miRs) indicated by the databases as targeting the signaling pathway of the type-1 insulin-like growth factor receptor (IGF-IR). Most of the miRs tested had multiple targets, as expected, leading to cell death. However, miR145 seemed to affect its tumor suppressor activity largely by downregulating the docking protein of the IGF-IR, the insulin receptor substrate-1 (IRS-1). These results suggest that, despite the many targets provided by the databases, in some cases a single target can be predominant in determining the end results.

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“…Within the limited range of environmental perturbations in most experiments, canalization may not be particularly important, but, in the evolutionary timescale, it may be crucial. Indeed, microRNAs have increasingly attracted attention as candidates for canalizing agents Cui et al 2006Cui et al , 2007Hornstein and Shomron 2006;Li et al 2006;Choi et al 2007;Tsang et al 2007;Varghese and Cohen 2007;Martinez et al 2008). …”

Section: Mirnas-their Paradoxical Function and Evolutionmentioning

confidence: 99%

Evolution under canalization and the dual roles of microRNAs—A hypothesis

Wu¹,

Shen²,

Tang³

2009

Genome Res.

144

160

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Canalization refers to the process by which phenotypes are stabilized within species. Evolution by natural selection can proceed efficiently only when phenotypes are canalized. The existence and identity of canalizing genes have thus been an important, but controversial topic. Recent evidence has increasingly hinted that microRNAs may be involved in canalizing gene expression. Their paradoxical properties (e.g., strongly conserved but functionally dispensable) suggest unconventional regulatory roles. We synthesized published and unpublished results and hypothesize that miRNAs may have dual functions-in gene expression tuning and in expression buffering. In tuning, miRNAs modify the mean expression level of their targets, but in buffering they merely reduce the variance around a preset mean. In light of the constant emergence of new miRNAs, we further discuss the relative importance of these two functions in evolution.Living organisms process as much information and execute as many instructions as any high-power computers normally do. The difference is that living organisms carry out the tasks under extremely variable environments, whereas no computers are made to withstand even moderate fluctuations in voltage input. Living things must be able to dampen variable inputs (in nutrition, temperature, humidity, genetic background, etc.) to achieve the remarkable stability in the output (development, physiological responses, gene expression, etc.). This phenomenon is the essence of biological homeostasis.Darwin's The Origin of Species (Darwin 1859), on the other hand, is about evolutionary changes. On the surface, evolutionary changes and phenotypic stability may seem like antithetical concepts, but in the language of genetics they are really two sides of the same issue. Evolution by natural selection can proceed only when biological systems are reasonably stable. Imagine a system in which phenotypic manifestation is highly variable. In it natural selection cannot easily distinguish one genotype from another and would have low efficacy. The original nongenetic version of the Darwinian theory encountered many difficulties. One of them was the blending of genetic materials, potentially leading to the homogenization of phenotypes. The other resulted from the ignorance of the difference between genotype and phenotype and the puzzle over the existence of phenotypic variation. Fisher (1930) pointed out that, in Darwin's thinking, phenotypic variation should have been purged by natural selection-only the fittest should have remained.The relationship between evolution and biological homeostasis can best be expressed in quantitative genetic terms. Let V g and V e denote phenotypic variance due to genotypic and environmental effect, respectively. V g 3 e is the interactive term between gene and environment. The total phenotypic variance, V t , can be expressed as follows:For simplicity, we assume no dominance here, but the general principle is the same in more complex systems. Any mechanism of biological homeostasis should redu...

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Principles of microRNA regulation of a human cellular signaling network

Cited by 334 publications

References 24 publications

MiRNA Synergistic Network Construction and Enrichment Analysis for Common Target Genes in Small-cell Lung Cancer

MiRNA Synergistic Network Construction and Enrichment Analysis for Common Target Genes in Small-cell Lung Cancer

Growth inhibition by microRNAs that target the insulin receptor substrate-1

Evolution under canalization and the dual roles of microRNAs—A hypothesis

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