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Expression patterns of microRNAs associated with CML phases and their disease related targets.

Machová Poláková K, Lopotová T, Klamová H, Burda P, Trněný M, Stopka T, Moravcová J - Mol. Cancer (2011)

Bottom Line: The expression deregulation of miR-150, miR-20a, miR-17, miR-19a, miR-103, miR-144, miR-155, miR-181a, miR-221 and miR-222 in CML was confirmed by real-time quantitative PCR.In silico analyses identified targeted genes of these miRNAs encoding proteins that are involved in cell cycle and growth regulation as well as several key signaling pathways such as of mitogen activated kinase-like protein (MAPK), epidermal growth factor receptor (EGFR, ERBB), transforming growth factor beta (TGFB1) and tumor protein p53 that are all related to CML.Decreased levels of miR-150 were detected in patients at diagnosis, in blast crisis and 67% of hematological relapses and showed significant negative correlation with miR-150 proved target MYB and with BCR-ABL transcript level.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Hematology and Blood Transfusion, Prague, U Nemocnice 1, 128 20, Czech Republic. katerina.machova@uhkt.cz

ABSTRACT

Background: MicroRNAs are important regulators of transcription in hematopoiesis. Their expression deregulations were described in association with pathogenesis of some hematological malignancies. This study provides integrated microRNA expression profiling at different phases of chronic myeloid leukemia (CML) with the aim to identify microRNAs associated with CML pathogenesis. The functions of in silico filtered targets are in this report annotated and discussed in relation to CML pathogenesis.

Results: Using microarrays we identified differential expression profiles of 49 miRNAs in CML patients at diagnosis, in hematological relapse, therapy failure, blast crisis and major molecular response. The expression deregulation of miR-150, miR-20a, miR-17, miR-19a, miR-103, miR-144, miR-155, miR-181a, miR-221 and miR-222 in CML was confirmed by real-time quantitative PCR. In silico analyses identified targeted genes of these miRNAs encoding proteins that are involved in cell cycle and growth regulation as well as several key signaling pathways such as of mitogen activated kinase-like protein (MAPK), epidermal growth factor receptor (EGFR, ERBB), transforming growth factor beta (TGFB1) and tumor protein p53 that are all related to CML. Decreased levels of miR-150 were detected in patients at diagnosis, in blast crisis and 67% of hematological relapses and showed significant negative correlation with miR-150 proved target MYB and with BCR-ABL transcript level.

Conclusions: This study uncovers microRNAs that are potentially involved in CML and the annotated functions of in silico filtered targets of selected miRNAs outline mechanisms whereby microRNAs may be involved in CML pathogenesis.

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Hierarchical clustering analysis of expression data of 49 microRNAs from microarray analysis. Seven miRNAs are not displayed due to signal at the background level in at least one of the pools analyzed.
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Figure 1: Hierarchical clustering analysis of expression data of 49 microRNAs from microarray analysis. Seven miRNAs are not displayed due to signal at the background level in at least one of the pools analyzed.

Mentions: Microarray analysis in CML resulted in the detection of 56 differentially expressed miRNAs (samples vs. control). Figure 1 shows three main gene clusters (clusters I, II, III) of altogether 49 miRNAs. A markedly (more than 1.5 fold; others are not indicated here) increased level over the control was found in BC pool for miR-19a, miR-19b, miR-221, miR-126, miR-106a, miR-17, miR-20a and miR-222 that belong to the cluster I. A distant gene cluster II grouped down-regulated miRNAs in BC; more than 1.5 fold change was detected for miR-24, miR-29b, miR-26b, miR-107, miR-103, miR-150, miR-451. The cluster III consisted of miRNAs with increased level in MMR; more than 1.5-fold change was found for miR-663, miR-638 and miR-720.


Expression patterns of microRNAs associated with CML phases and their disease related targets.

Machová Poláková K, Lopotová T, Klamová H, Burda P, Trněný M, Stopka T, Moravcová J - Mol. Cancer (2011)

Hierarchical clustering analysis of expression data of 49 microRNAs from microarray analysis. Seven miRNAs are not displayed due to signal at the background level in at least one of the pools analyzed.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3102634&req=5

Figure 1: Hierarchical clustering analysis of expression data of 49 microRNAs from microarray analysis. Seven miRNAs are not displayed due to signal at the background level in at least one of the pools analyzed.
Mentions: Microarray analysis in CML resulted in the detection of 56 differentially expressed miRNAs (samples vs. control). Figure 1 shows three main gene clusters (clusters I, II, III) of altogether 49 miRNAs. A markedly (more than 1.5 fold; others are not indicated here) increased level over the control was found in BC pool for miR-19a, miR-19b, miR-221, miR-126, miR-106a, miR-17, miR-20a and miR-222 that belong to the cluster I. A distant gene cluster II grouped down-regulated miRNAs in BC; more than 1.5 fold change was detected for miR-24, miR-29b, miR-26b, miR-107, miR-103, miR-150, miR-451. The cluster III consisted of miRNAs with increased level in MMR; more than 1.5-fold change was found for miR-663, miR-638 and miR-720.

Bottom Line: The expression deregulation of miR-150, miR-20a, miR-17, miR-19a, miR-103, miR-144, miR-155, miR-181a, miR-221 and miR-222 in CML was confirmed by real-time quantitative PCR.In silico analyses identified targeted genes of these miRNAs encoding proteins that are involved in cell cycle and growth regulation as well as several key signaling pathways such as of mitogen activated kinase-like protein (MAPK), epidermal growth factor receptor (EGFR, ERBB), transforming growth factor beta (TGFB1) and tumor protein p53 that are all related to CML.Decreased levels of miR-150 were detected in patients at diagnosis, in blast crisis and 67% of hematological relapses and showed significant negative correlation with miR-150 proved target MYB and with BCR-ABL transcript level.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Hematology and Blood Transfusion, Prague, U Nemocnice 1, 128 20, Czech Republic. katerina.machova@uhkt.cz

ABSTRACT

Background: MicroRNAs are important regulators of transcription in hematopoiesis. Their expression deregulations were described in association with pathogenesis of some hematological malignancies. This study provides integrated microRNA expression profiling at different phases of chronic myeloid leukemia (CML) with the aim to identify microRNAs associated with CML pathogenesis. The functions of in silico filtered targets are in this report annotated and discussed in relation to CML pathogenesis.

Results: Using microarrays we identified differential expression profiles of 49 miRNAs in CML patients at diagnosis, in hematological relapse, therapy failure, blast crisis and major molecular response. The expression deregulation of miR-150, miR-20a, miR-17, miR-19a, miR-103, miR-144, miR-155, miR-181a, miR-221 and miR-222 in CML was confirmed by real-time quantitative PCR. In silico analyses identified targeted genes of these miRNAs encoding proteins that are involved in cell cycle and growth regulation as well as several key signaling pathways such as of mitogen activated kinase-like protein (MAPK), epidermal growth factor receptor (EGFR, ERBB), transforming growth factor beta (TGFB1) and tumor protein p53 that are all related to CML. Decreased levels of miR-150 were detected in patients at diagnosis, in blast crisis and 67% of hematological relapses and showed significant negative correlation with miR-150 proved target MYB and with BCR-ABL transcript level.

Conclusions: This study uncovers microRNAs that are potentially involved in CML and the annotated functions of in silico filtered targets of selected miRNAs outline mechanisms whereby microRNAs may be involved in CML pathogenesis.

Show MeSH
Related in: MedlinePlus