Combinatorial Network of Primary and Secondary MicroRNA-driven Regulatory Mechanisms

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2009 Aug 13

PMID 19671526

Citations 40

Authors

Kang Tu

Hui Yu

You-Jia Hua

Yuan-Yuan Li

Lei Liu

Lu Xie

Yi-Xue Li

Affiliations

Soon will be listed here.

Abstract

Recent miRNA transfection experiments show strong evidence that miRNAs influence not only their target but also non-target genes; the precise mechanism of the extended regulatory effects of miRNAs remains to be elucidated. A hypothetical two-layer regulatory network in which transcription factors (TFs) function as important mediators of miRNA-initiated regulatory effects was envisioned, and a comprehensive strategy was developed to map such miRNA-centered regulatory cascades. Given gene expression profiles after miRNA-perturbation, along with putative miRNA-gene and TF-gene regulatory relationships, highly likely degraded targets were fetched by a non-parametric statistical test; miRNA-regulated TFs and their downstream targets were mined out through linear regression modeling. When applied to 53 expression datasets, this strategy discovered combinatorial regulatory networks centered around 19 miRNAs. A tumor-related regulatory network was diagrammed as an example, with the important tumor-related regulators TP53 and MYC playing hub connector roles. A web server is provided for query and analysis of all reported data in this article. Our results reinforce the growing awareness that non-coding RNAs may play key roles in the transcription regulatory network. Our strategy could be applied to reveal conditional regulatory pathways in many more cellular contexts.

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