Identification of acute myeloid leukaemia associated microRNA expression patterns

MicroRNAs (miRNAs) play an important role in cellular differentiation and cancer pathogenesis. This study analysed the expression of 154 human miRNAs in acute myeloid leukaemia (AML) and control samples using a stem‐loop real‐time reverse transcription polymerase chain reaction approach. Global patterns of miRNA expression in AML, normal bone marrow (NBM) and CD34+ progenitor cells allowed correct class predictions similar to whole genome microarray expression analyses that were performed at the same time. At single miRNA species level, MIRN23B was repressed in AML specimens compared to NBM and purified CD34+ haematopoietic progenitor cells. In contrast, the MIRN221/MIRN222 cluster and MIRN34A were expressed at significantly higher levels in AML blasts. Patients with high MIRN221/MIRN222 expression showed low levels of KIT RNA and protein expression but the correlation between kit protein and KIT mRNA was significantly stronger than the correlation of either one with MIRN221/MIRN222. A global analysis between miRNA expression levels and mRNA expression of predicted target genes revealed only weak associations in the majority of miRNA species. Nonetheless, the presence of two or more miRNA binding sites within the mRNA was usually associated with a decrease in mRNA levels. Taken together, these findings provide evidence that specific miRNA expression patterns exist in AML.

[1]  Reuven Agami,et al.  Regulation of the p27Kip1 tumor suppressor by miR‐221 and miR‐222 promotes cancer cell proliferation , 2007 .

[2]  R. Stallings,et al.  MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells , 2007, Oncogene.

[3]  V. Tarasov,et al.  Differential Regulation of microRNAs by p53 Revealed by Massively Parallel Sequencing: miR-34a is a p53 Target That Induces Apoptosis and G1-arrest , 2007, Cell cycle.

[4]  C. Croce,et al.  MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia , 2007, Oncogene.

[5]  Michael A. Beer,et al.  Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. , 2007, Molecular cell.

[6]  Moshe Oren,et al.  Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. , 2007, Molecular cell.

[7]  C. Lawrie.  MicroRNAs and haematology: small molecules, big function , 2007, British journal of haematology.

[8]  T Chaplin,et al.  MicroRNA miR-181a correlates with morphological sub-class of acute myeloid leukaemia and the expression of its target genes in global genome-wide analysis , 2007, Leukemia.

[9]  B. Kroesen,et al.  The role of microRNAs in normal hematopoiesis and hematopoietic malignancies , 2006, Leukemia.

[10]  G. Hutvagner,et al.  Principles and effects of microRNA-mediated post-transcriptional gene regulation , 2006, Oncogene.

[11]  Sven Diederichs,et al.  Sequence variations of microRNAs in human cancer: alterations in predicted secondary structure do not affect processing. , 2006, Cancer research.

[12]  C. Croce,et al.  MicroRNA deregulation in human thyroid papillary carcinomas. , 2006, Endocrine-related cancer.

[13]  J Philip McCoy,et al.  Hematopoietic-specific microRNA expression in human cells. , 2006, Leukemia research.

[14]  F. Slack,et al.  Oncomirs — microRNAs with a role in cancer , 2006, Nature Reviews Cancer.

[15]  Lu Zhang,et al.  Large scale real-time PCR validation on gene expression measurements from two commercial long-oligonucleotide microarrays , 2006, BMC Genomics.

[16]  N. Rajewsky,et al.  Cell-type-specific signatures of microRNAs on target mRNA expression. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[17]  C. Burge,et al.  The Widespread Impact of Mammalian MicroRNAs on mRNA Repression and Evolution , 2005, Science.

[18]  C. Croce,et al.  MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Alessandro Fatica,et al.  A Minicircuitry Comprised of MicroRNA-223 and Transcription Factors NFI-A and C/EBPα Regulates Human Granulopoiesis , 2005, Cell.

[20]  K. Livak,et al.  Real-time quantification of microRNAs by stem–loop RT–PCR , 2005, Nucleic acids research.

[21]  Muller Fabbri,et al.  A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. , 2005, The New England journal of medicine.

[22]  G. Maira,et al.  Extensive modulation of a set of microRNAs in primary glioblastoma. , 2005, Biochemical and biophysical research communications.

[23]  A. Pasquinelli,et al.  Regulation by let-7 and lin-4 miRNAs Results in Target mRNA Degradation , 2005, Cell.

[24]  H. Horvitz,et al.  MicroRNA expression profiles classify human cancers , 2005, Nature.

[25]  Shuang Huang,et al.  Involvement of MicroRNA in AU-Rich Element-Mediated mRNA Instability , 2005, Cell.

[26]  F. Slack,et al.  RAS Is Regulated by the let-7 MicroRNA Family , 2005, Cell.

[27]  J. Castle,et al.  Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs , 2005, Nature.

[28]  D. Bartel,et al.  MicroRNA-Directed Cleavage of HOXB8 mRNA , 2004, Science.

[29]  John G Doench,et al.  Specificity of microRNA target selection in translational repression. , 2004, Genes & development.

[30]  Arndt Borkhardt,et al.  High expression of precursor microRNA‐155/BIC RNA in children with Burkitt lymphoma , 2004, Genes, chromosomes & cancer.

[31]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[32]  D. Bartel,et al.  MicroRNAs Modulate Hematopoietic Lineage Differentiation , 2004, Science.

[33]  C. Burge,et al.  Vertebrate MicroRNA Genes , 2003, Science.

[34]  A. Ganser,et al.  Tumor suppressor genes in normal and malignant hematopoiesis , 2002, Oncogene.

[35]  Reuven Agami,et al.  Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. , 2007, The EMBO journal.