In-depth characterization of the microRNA transcriptome in a leukemia progression model Export

@article{citeulike:4080315, abstract = {10.1101/gr.077578.108 MicroRNAs (miRNAs) have been shown to play important roles in physiological as well as multiple malignant processes, including acute myeloid leukemia (AML). In an effort to gain further insight into the role of miRNAs in AML, we have applied the Illumina massively parallel sequencing platform to carry out an in-depth analysis of the miRNA transcriptome in a murine leukemia progression model. This model simulates the stepwise conversion of a myeloid progenitor cell by an engineered overexpression of the nucleoporin 98 ()–homeobox fusion gene (ND13), to aggressive AML inducing cells upon transduction with the oncogenic collaborator From this data set, we identified 307 miRNA/miRNA* species in the ND13 cells and 306 miRNA/miRNA* species in ND13+Meis1 cells, corresponding to 223 and 219 miRNA genes. Sequence counts varied between two and 136,558, indicating a remarkable expression range between the detected miRNA species. The large number of miRNAs expressed and the nature of differential expression suggest that leukemic progression as modeled here is dictated by the repertoire of shared, but differentially expressed miRNAs. Our finding of extensive sequence variations (isomiRs) for almost all miRNA and miRNA* species adds additional complexity to the miRNA transcriptome. A stringent target prediction analysis coupled with in vitro target validation revealed the potential for miRNA-mediated release of oncogenes that facilitates leukemic progression from the preleukemic to leukemia inducing state. Finally, 55 novel miRNAs species were identified in our data set, adding further complexity to the emerging world of small RNAs.}, author = {Kuchenbauer, Florian and Morin, Ryan D. and Argiropoulos, Bob and Petriv, Oleh I. and Griffith, Malachi and Heuser, Michael and Yung, Eric and Piper, Jessica and Delaney, Allen and Prabhu, Anna-Liisa and Zhao, Yongjun and Mcdonald, Helen and Zeng, Thomas and Hirst, Martin and Hansen, Carl L. and Marra, Marco A. and Humphries, R. Keith}, citeulike-article-id = {4080315}, citeulike-linkout-0 = {http://dx.doi.org/10.1101/gr.077578.108}, citeulike-linkout-1 = {http://genome.cshlp.org/content/18/11/1787.abstract}, citeulike-linkout-2 = {http://genome.cshlp.org/content/18/11/1787.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/18849523}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=18849523}, doi = {10.1101/gr.077578.108}, issn = {1088-9051}, journal = {Genome Research}, keywords = {deep\_sequencing, leukemia, mirna, progression}, month = {November}, number = {11}, pages = {1787--1797}, posted-at = {2009-02-23 10:57:42}, priority = {2}, title = {In-depth characterization of the microRNA transcriptome in a leukemia progression model}, url = {http://dx.doi.org/10.1101/gr.077578.108}, volume = {18}, year = {2008} }

TY - JOUR ID - citeulike:4080315 L3 - citeulike-article-id:4080315 N2 - 10.1101/gr.077578.108 MicroRNAs (miRNAs) have been shown to play important roles in physiological as well as multiple malignant processes, including acute myeloid leukemia (AML). In an effort to gain further insight into the role of miRNAs in AML, we have applied the Illumina massively parallel sequencing platform to carry out an in-depth analysis of the miRNA transcriptome in a murine leukemia progression model. This model simulates the stepwise conversion of a myeloid progenitor cell by an engineered overexpression of the nucleoporin 98 ()–homeobox fusion gene (ND13), to aggressive AML inducing cells upon transduction with the oncogenic collaborator From this data set, we identified 307 miRNA/miRNA* species in the ND13 cells and 306 miRNA/miRNA* species in ND13+Meis1 cells, corresponding to 223 and 219 miRNA genes. Sequence counts varied between two and 136,558, indicating a remarkable expression range between the detected miRNA species. The large number of miRNAs expressed and the nature of differential expression suggest that leukemic progression as modeled here is dictated by the repertoire of shared, but differentially expressed miRNAs. Our finding of extensive sequence variations (isomiRs) for almost all miRNA and miRNA* species adds additional complexity to the miRNA transcriptome. A stringent target prediction analysis coupled with in vitro target validation revealed the potential for miRNA-mediated release of oncogenes that facilitates leukemic progression from the preleukemic to leukemia inducing state. Finally, 55 novel miRNAs species were identified in our data set, adding further complexity to the emerging world of small RNAs. IS - 11 JF - Genome Research SN - 1088-9051 EP - 1797 TI - In-depth characterization of the microRNA transcriptome in a leukemia progression model VL - 18 SP - 1787 KW - deep_sequencing KW - leukemia KW - mirna KW - progression AU - Kuchenbauer, Florian AU - Morin, Ryan AU - Argiropoulos, Bob AU - Petriv, Oleh AU - Griffith, Malachi AU - Heuser, Michael AU - Yung, Eric AU - Piper, Jessica AU - Delaney, Allen AU - Prabhu, Anna-Liisa AU - Zhao, Yongjun AU - Mcdonald, Helen AU - Zeng, Thomas AU - Hirst, Martin AU - Hansen, Carl AU - Marra, Marco AU - Humphries, Keith PY - 2008/11// UR - http://dx.doi.org/10.1101/gr.077578.108 ER -