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MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia.
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| Zeitschriftentitel: | Blood |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | Blood, 108, 2006, 11, S. 4197-4197 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Hematology
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| Schlagwörter: |
| author_facet |
Nigten, Jeannet Knops, Ruth Nikoloski, Gorica de Witte, Theo M. van der Reijden, Bert A. Jansen, Joop H. Nigten, Jeannet Knops, Ruth Nikoloski, Gorica de Witte, Theo M. van der Reijden, Bert A. Jansen, Joop H. |
|---|---|
| author |
Nigten, Jeannet Knops, Ruth Nikoloski, Gorica de Witte, Theo M. van der Reijden, Bert A. Jansen, Joop H. |
| spellingShingle |
Nigten, Jeannet Knops, Ruth Nikoloski, Gorica de Witte, Theo M. van der Reijden, Bert A. Jansen, Joop H. Blood MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. Cell Biology Hematology Immunology Biochemistry |
| author_sort |
nigten, jeannet |
| spelling |
Nigten, Jeannet Knops, Ruth Nikoloski, Gorica de Witte, Theo M. van der Reijden, Bert A. Jansen, Joop H. 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v108.11.4197.4197 <jats:title>Abstract</jats:title> <jats:p>The discovery of the microRNA (miRNA) molecules has led to new insights into the regulation of gene expression. They are able to bind specific mRNA sequences, and due to inhibition of translation or mRNA degradation, miRNAs cause downregulation of their target genes. To date, several hundreds of unique human miRNAs have been described. So far, for only few of them the target mRNAs have been experimentally confirmed. MiRNAs have been linked to several important biological processes as early stage development, cell growth, cell differentiation and apoptosis. In addition, impaired miRNA expression has been implicated in tumorigenesis. Leukemia is often associated with mutated transcription factors and, as a consequence, deregulated gene expression and impaired proliferation and differentiation. Acute Promyelocytic Leukemia (APL), is characterised by the expression of the mutated transcription factor PML-RARα, which may interfere with the normal function of the retinoic acid receptor α (RARα), a nuclear hormone receptor that acts as a ligand-dependent transcription factor. APL is uniquely sensitive to treatment with the RARα ligand, all-trans retinoic acid (ATRA), which results in the expression of genes that induce terminal granulocytic differentiation of the leukemic blasts. To investigate whether miRNA expression is regulated by ATRA in APL, we performed Taqman miRNA assays for 157 different mature miRNAs in the APL cell line NB4 before and after treatment with ATRA. We found that ATRA induced a more than 10 fold upregulation of 18 miRNAs and a more than 10 fold downregulation of 2 miRNAs. These expression patterns were confirmed in primary APL patient cells before and after treatment with ATRA. To study whether the miRNA expression pattern was dependent on the PML-RARα fusion protein, we used U937 cells stably transfected with a zinc-inducible PML-RARα expression cassette (U937PR9, a kind gift of Dr Pelicci). Upon ATRA treatment, we found that several miRNAs were only induced in the presence of PML-RARα, suggesting that PML-RARα is implicated in the expression of these miRNAs. To investigate whether the PML-RARα fusion protein binds to the endogenous miRNA genes chromatin immunoprecipitation assays were performed with PML-RARα transfected 293 cells. We demonstrated the presence of PML-RARα protein on the miRNA genes. This indicates that the oncoprotein PML-RARα directly influences the expression of these miRNAs. The function of the PML-RARα targeted miRNAs in APL cell differentiation is currently being studied using retroviral expression vectors.</jats:p> MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. Blood |
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| title |
MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. |
| title_unstemmed |
MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. |
| title_full |
MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. |
| title_fullStr |
MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. |
| title_full_unstemmed |
MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. |
| title_short |
MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. |
| title_sort |
mirna transcription is regulated by the pml-rarα oncoprotein in acute promyelocytic leukemia. |
| topic |
Cell Biology Hematology Immunology Biochemistry |
| url |
http://dx.doi.org/10.1182/blood.v108.11.4197.4197 |
| publishDate |
2006 |
| physical |
4197-4197 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>The discovery of the microRNA (miRNA) molecules has led to new insights into the regulation of gene expression. They are able to bind specific mRNA sequences, and due to inhibition of translation or mRNA degradation, miRNAs cause downregulation of their target genes. To date, several hundreds of unique human miRNAs have been described. So far, for only few of them the target mRNAs have been experimentally confirmed. MiRNAs have been linked to several important biological processes as early stage development, cell growth, cell differentiation and apoptosis. In addition, impaired miRNA expression has been implicated in tumorigenesis. Leukemia is often associated with mutated transcription factors and, as a consequence, deregulated gene expression and impaired proliferation and differentiation. Acute Promyelocytic Leukemia (APL), is characterised by the expression of the mutated transcription factor PML-RARα, which may interfere with the normal function of the retinoic acid receptor α (RARα), a nuclear hormone receptor that acts as a ligand-dependent transcription factor. APL is uniquely sensitive to treatment with the RARα ligand, all-trans retinoic acid (ATRA), which results in the expression of genes that induce terminal granulocytic differentiation of the leukemic blasts. To investigate whether miRNA expression is regulated by ATRA in APL, we performed Taqman miRNA assays for 157 different mature miRNAs in the APL cell line NB4 before and after treatment with ATRA. We found that ATRA induced a more than 10 fold upregulation of 18 miRNAs and a more than 10 fold downregulation of 2 miRNAs. These expression patterns were confirmed in primary APL patient cells before and after treatment with ATRA. To study whether the miRNA expression pattern was dependent on the PML-RARα fusion protein, we used U937 cells stably transfected with a zinc-inducible PML-RARα expression cassette (U937PR9, a kind gift of Dr Pelicci). Upon ATRA treatment, we found that several miRNAs were only induced in the presence of PML-RARα, suggesting that PML-RARα is implicated in the expression of these miRNAs. To investigate whether the PML-RARα fusion protein binds to the endogenous miRNA genes chromatin immunoprecipitation assays were performed with PML-RARα transfected 293 cells. We demonstrated the presence of PML-RARα protein on the miRNA genes. This indicates that the oncoprotein PML-RARα directly influences the expression of these miRNAs. The function of the PML-RARα targeted miRNAs in APL cell differentiation is currently being studied using retroviral expression vectors.</jats:p> |
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| author | Nigten, Jeannet, Knops, Ruth, Nikoloski, Gorica, de Witte, Theo M., van der Reijden, Bert A., Jansen, Joop H. |
| author_facet | Nigten, Jeannet, Knops, Ruth, Nikoloski, Gorica, de Witte, Theo M., van der Reijden, Bert A., Jansen, Joop H., Nigten, Jeannet, Knops, Ruth, Nikoloski, Gorica, de Witte, Theo M., van der Reijden, Bert A., Jansen, Joop H. |
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| description | <jats:title>Abstract</jats:title> <jats:p>The discovery of the microRNA (miRNA) molecules has led to new insights into the regulation of gene expression. They are able to bind specific mRNA sequences, and due to inhibition of translation or mRNA degradation, miRNAs cause downregulation of their target genes. To date, several hundreds of unique human miRNAs have been described. So far, for only few of them the target mRNAs have been experimentally confirmed. MiRNAs have been linked to several important biological processes as early stage development, cell growth, cell differentiation and apoptosis. In addition, impaired miRNA expression has been implicated in tumorigenesis. Leukemia is often associated with mutated transcription factors and, as a consequence, deregulated gene expression and impaired proliferation and differentiation. Acute Promyelocytic Leukemia (APL), is characterised by the expression of the mutated transcription factor PML-RARα, which may interfere with the normal function of the retinoic acid receptor α (RARα), a nuclear hormone receptor that acts as a ligand-dependent transcription factor. APL is uniquely sensitive to treatment with the RARα ligand, all-trans retinoic acid (ATRA), which results in the expression of genes that induce terminal granulocytic differentiation of the leukemic blasts. To investigate whether miRNA expression is regulated by ATRA in APL, we performed Taqman miRNA assays for 157 different mature miRNAs in the APL cell line NB4 before and after treatment with ATRA. We found that ATRA induced a more than 10 fold upregulation of 18 miRNAs and a more than 10 fold downregulation of 2 miRNAs. These expression patterns were confirmed in primary APL patient cells before and after treatment with ATRA. To study whether the miRNA expression pattern was dependent on the PML-RARα fusion protein, we used U937 cells stably transfected with a zinc-inducible PML-RARα expression cassette (U937PR9, a kind gift of Dr Pelicci). Upon ATRA treatment, we found that several miRNAs were only induced in the presence of PML-RARα, suggesting that PML-RARα is implicated in the expression of these miRNAs. To investigate whether the PML-RARα fusion protein binds to the endogenous miRNA genes chromatin immunoprecipitation assays were performed with PML-RARα transfected 293 cells. We demonstrated the presence of PML-RARα protein on the miRNA genes. This indicates that the oncoprotein PML-RARα directly influences the expression of these miRNAs. The function of the PML-RARα targeted miRNAs in APL cell differentiation is currently being studied using retroviral expression vectors.</jats:p> |
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| imprint | American Society of Hematology, 2006 |
| imprint_str_mv | American Society of Hematology, 2006 |
| institution | DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275 |
| issn | 0006-4971, 1528-0020 |
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| spelling | Nigten, Jeannet Knops, Ruth Nikoloski, Gorica de Witte, Theo M. van der Reijden, Bert A. Jansen, Joop H. 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v108.11.4197.4197 <jats:title>Abstract</jats:title> <jats:p>The discovery of the microRNA (miRNA) molecules has led to new insights into the regulation of gene expression. They are able to bind specific mRNA sequences, and due to inhibition of translation or mRNA degradation, miRNAs cause downregulation of their target genes. To date, several hundreds of unique human miRNAs have been described. So far, for only few of them the target mRNAs have been experimentally confirmed. MiRNAs have been linked to several important biological processes as early stage development, cell growth, cell differentiation and apoptosis. In addition, impaired miRNA expression has been implicated in tumorigenesis. Leukemia is often associated with mutated transcription factors and, as a consequence, deregulated gene expression and impaired proliferation and differentiation. Acute Promyelocytic Leukemia (APL), is characterised by the expression of the mutated transcription factor PML-RARα, which may interfere with the normal function of the retinoic acid receptor α (RARα), a nuclear hormone receptor that acts as a ligand-dependent transcription factor. APL is uniquely sensitive to treatment with the RARα ligand, all-trans retinoic acid (ATRA), which results in the expression of genes that induce terminal granulocytic differentiation of the leukemic blasts. To investigate whether miRNA expression is regulated by ATRA in APL, we performed Taqman miRNA assays for 157 different mature miRNAs in the APL cell line NB4 before and after treatment with ATRA. We found that ATRA induced a more than 10 fold upregulation of 18 miRNAs and a more than 10 fold downregulation of 2 miRNAs. These expression patterns were confirmed in primary APL patient cells before and after treatment with ATRA. To study whether the miRNA expression pattern was dependent on the PML-RARα fusion protein, we used U937 cells stably transfected with a zinc-inducible PML-RARα expression cassette (U937PR9, a kind gift of Dr Pelicci). Upon ATRA treatment, we found that several miRNAs were only induced in the presence of PML-RARα, suggesting that PML-RARα is implicated in the expression of these miRNAs. To investigate whether the PML-RARα fusion protein binds to the endogenous miRNA genes chromatin immunoprecipitation assays were performed with PML-RARα transfected 293 cells. We demonstrated the presence of PML-RARα protein on the miRNA genes. This indicates that the oncoprotein PML-RARα directly influences the expression of these miRNAs. The function of the PML-RARα targeted miRNAs in APL cell differentiation is currently being studied using retroviral expression vectors.</jats:p> MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. Blood |
| spellingShingle | Nigten, Jeannet, Knops, Ruth, Nikoloski, Gorica, de Witte, Theo M., van der Reijden, Bert A., Jansen, Joop H., Blood, MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia., Cell Biology, Hematology, Immunology, Biochemistry |
| title | MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. |
| title_full | MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. |
| title_fullStr | MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. |
| title_full_unstemmed | MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. |
| title_short | MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. |
| title_sort | mirna transcription is regulated by the pml-rarα oncoprotein in acute promyelocytic leukemia. |
| title_unstemmed | MiRNA Transcription Is Regulated by the PML-RARα Oncoprotein in Acute Promyelocytic Leukemia. |
| topic | Cell Biology, Hematology, Immunology, Biochemistry |
| url | http://dx.doi.org/10.1182/blood.v108.11.4197.4197 |