BACKGROUND: The expression of microRNAs (miRNAs) is deregulated in acute myeloid leukemia (AML), but the corresponding functional miRNA-controlled pathways are poorly understood. Integration of messenger RNA (mRNA) and miRNA expression profiling may allow the identification of functional links between the whole transcriptome and microRNome that are involved in myeloid leukemogenesis. METHODS: We integrated miRNA and mRNA expression profiles obtained from 48 newly diagnosed AML patients by using 2 different microarray platforms and performed correlation, gene ontology, and network analysis. Experimental validation was also performed in AML cell lines using miRNA oligonucleotide mimics and functional assays. RESULTS: Our analysis identified a strong positive correlation between HOX-related genes and miR-10 and miR-20a. Furthermore, we observed a negative correlation between miR-181a and miR-181b, miR-155, and miR-146 expression with that of genes involved in immunity and inflammation (eg, IRF7 and TLR4) and a positive correlation between miR-23a, miR-26a, miR-128a, and miR-145 expression with that of proapoptotic genes (eg, BIM and PTEN). These correlations were confirmed by gene ontology analyses, which revealed the enrichment of members of the homeobox, immunity and inflammation, and apoptosis biological processes. Furthermore, we validated experimentally the association of miR-145, miR-26a, and miR-128a with apoptosis in AML. CONCLUSION: Our results indicate that by integrating the transcriptome and microRNome in AML cells, it is possible to identify previously unidentified putative functional miRNA-mRNA interactions in AML.
BACKGROUND: The expression of microRNAs (miRNAs) is deregulated in acute myeloid leukemia (AML), but the corresponding functional miRNA-controlled pathways are poorly understood. Integration of messenger RNA (mRNA) and miRNA expression profiling may allow the identification of functional links between the whole transcriptome and microRNome that are involved in myeloid leukemogenesis. METHODS: We integrated miRNA and mRNA expression profiles obtained from 48 newly diagnosed AMLpatients by using 2 different microarray platforms and performed correlation, gene ontology, and network analysis. Experimental validation was also performed in AML cell lines using miRNA oligonucleotide mimics and functional assays. RESULTS: Our analysis identified a strong positive correlation between HOX-related genes and miR-10 and miR-20a. Furthermore, we observed a negative correlation between miR-181a and miR-181b, miR-155, and miR-146 expression with that of genes involved in immunity and inflammation (eg, IRF7 and TLR4) and a positive correlation between miR-23a, miR-26a, miR-128a, and miR-145 expression with that of proapoptotic genes (eg, BIM and PTEN). These correlations were confirmed by gene ontology analyses, which revealed the enrichment of members of the homeobox, immunity and inflammation, and apoptosis biological processes. Furthermore, we validated experimentally the association of miR-145, miR-26a, and miR-128a with apoptosis in AML. CONCLUSION: Our results indicate that by integrating the transcriptome and microRNome in AML cells, it is possible to identify previously unidentified putative functional miRNA-mRNA interactions in AML.
Authors: Azra Krek; Dominic Grün; Matthew N Poy; Rachel Wolf; Lauren Rosenberg; Eric J Epstein; Philip MacMenamin; Isabelle da Piedade; Kristin C Gunsalus; Markus Stoffel; Nikolaus Rajewsky Journal: Nat Genet Date: 2005-04-03 Impact factor: 38.330
Authors: Nadia Felli; Laura Fontana; Elvira Pelosi; Rosanna Botta; Desirée Bonci; Francesco Facchiano; Francesca Liuzzi; Valentina Lulli; Ornella Morsilli; Simona Santoro; Mauro Valtieri; George Adrian Calin; Chang-Gong Liu; Antonio Sorrentino; Carlo M Croce; Cesare Peschle Journal: Proc Natl Acad Sci U S A Date: 2005-12-05 Impact factor: 11.205
Authors: Qi-Jing Li; Jacqueline Chau; Peter J R Ebert; Giselle Sylvester; Hyeyoung Min; Gwen Liu; Ravi Braich; Muthiah Manoharan; Juergen Soutschek; Petra Skare; Lawrence O Klein; Mark M Davis; Chang-Zheng Chen Journal: Cell Date: 2007-03-22 Impact factor: 41.582
Authors: Konstantin D Taganov; Mark P Boldin; Kuang-Jung Chang; David Baltimore Journal: Proc Natl Acad Sci U S A Date: 2006-08-02 Impact factor: 11.205
Authors: To-Ha Thai; Dinis Pedro Calado; Stefano Casola; K Mark Ansel; Changchun Xiao; Yingzi Xue; Andrew Murphy; David Frendewey; David Valenzuela; Jeffery L Kutok; Marc Schmidt-Supprian; Nikolaus Rajewsky; George Yancopoulos; Anjana Rao; Klaus Rajewsky Journal: Science Date: 2007-04-27 Impact factor: 47.728
Authors: M S Ostenfeld; J B Bramsen; P Lamy; S B Villadsen; N Fristrup; K D Sørensen; B Ulhøi; M Borre; J Kjems; L Dyrskjøt; T F Orntoft Journal: Oncogene Date: 2009-11-16 Impact factor: 9.867
Authors: Caifu Chen; Dana A Ridzon; Adam J Broomer; Zhaohui Zhou; Danny H Lee; Julie T Nguyen; Maura Barbisin; Nan Lan Xu; Vikram R Mahuvakar; Mark R Andersen; Kai Qin Lao; Kenneth J Livak; Karl J Guegler Journal: Nucleic Acids Res Date: 2005-11-27 Impact factor: 16.971
Authors: Annika C Russ; Sandrine Sander; Sonja C Lück; Katharina M Lang; Marion Bauer; Frank G Rücker; Hans A Kestler; Richard F Schlenk; Hartmut Döhner; Karlheinz Holzmann; Konstanze Döhner; Lars Bullinger Journal: Haematologica Date: 2011-08-31 Impact factor: 9.941
Authors: Pablo Letelier; Patricia García; Pamela Leal; Héctor Álvarez; Carmen Ili; Jaime López; Jonathan Castillo; Priscilla Brebi; Juan Carlos Roa Journal: Int J Clin Exp Pathol Date: 2014-04-15
Authors: K H Metzeler; K Maharry; J Kohlschmidt; S Volinia; K Mrózek; H Becker; D Nicolet; S P Whitman; J H Mendler; S Schwind; A-K Eisfeld; Y-Z Wu; B L Powell; T H Carter; M Wetzler; J E Kolitz; M R Baer; A J Carroll; R M Stone; M A Caligiuri; G Marcucci; C D Bloomfield Journal: Leukemia Date: 2013-06-14 Impact factor: 11.528