Combinatorial network of primary and secondary microRNA-driven regulatory mechanisms Export

@article{citeulike:5629589, 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. 10.1093/nar/gkp638}, author = {Tu, Kang and Yu, Hui and Hua, You-Jia and Li, Yuan-Yuan and Liu, Lei and Xie, Lu and Li, Yi-Xue}, citeulike-article-id = {5629589}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/nar/gkp638}, citeulike-linkout-1 = {http://nar.oxfordjournals.org/content/gkp638v1/.abstract}, citeulike-linkout-2 = {http://nar.oxfordjournals.org/content/gkp638v1/.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19671526}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19671526}, day = {1}, doi = {10.1093/nar/gkp638}, issn = {1362-4962}, journal = {Nucl. Acids Res.}, keywords = {mirna, network, primary, secondary, target\_genes}, month = {October}, number = {18}, pages = {5969--5980}, posted-at = {2009-10-23 10:03:46}, priority = {2}, title = {Combinatorial network of primary and secondary microRNA-driven regulatory mechanisms}, url = {http://dx.doi.org/10.1093/nar/gkp638}, volume = {37}, year = {2009} }

TY - JOUR ID - citeulike:5629589 L3 - citeulike-article-id:5629589 N2 - 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. 10.1093/nar/gkp638 IS - 18 JF - Nucl. Acids Res. SN - 1362-4962 EP - 5980 TI - Combinatorial network of primary and secondary microRNA-driven regulatory mechanisms VL - 37 SP - 5969 KW - mirna KW - network KW - primary KW - secondary KW - target_genes AU - Tu, Kang AU - Yu, Hui AU - Hua, You-Jia AU - Li, Yuan-Yuan AU - Liu, Lei AU - Xie, Lu AU - Li, Yi-Xue PY - 2009/10/01/ UR - http://dx.doi.org/10.1093/nar/gkp638 ER -