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Downregulation of Mir-31, Mir-155, and Mir-564 in Chronic Myeloid Leukemia Cells
BACKGROUND/AIMS: MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression and play an important role in cancer development and progression. However, little is known about the role of miRNAs in chronic myeloid leukemia (CML). Our objective is to decipher a miRNA expression...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325224/ https://www.ncbi.nlm.nih.gov/pubmed/22511990 http://dx.doi.org/10.1371/journal.pone.0035501 |
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author | Hershkovitz Rokah, Oshrat Granot, Galit Ovcharenko, Adelina Modai, Shira Pasmanik-Chor, Metsada Toren, Amos Shomron, Noam Shpilberg, Ofer |
author_facet | Hershkovitz Rokah, Oshrat Granot, Galit Ovcharenko, Adelina Modai, Shira Pasmanik-Chor, Metsada Toren, Amos Shomron, Noam Shpilberg, Ofer |
author_sort | Hershkovitz Rokah, Oshrat |
collection | PubMed |
description | BACKGROUND/AIMS: MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression and play an important role in cancer development and progression. However, little is known about the role of miRNAs in chronic myeloid leukemia (CML). Our objective is to decipher a miRNA expression signature associated with CML and to determine potential target genes and signaling pathways affected by these signature miRNAs. RESULTS: Using miRNA microarrays and miRNA real-time PCR we characterized the miRNAs expression profile of CML cell lines and patients in reference to non-CML cell lines and healthy blood. Of all miRNAs tested, miR-31, miR-155, and miR-564 were down-regulated in CML cells. Down-regulation of these miRNAs was dependent on BCR-ABL activity. We next analyzed predicted targets and affected pathways of the deregulated miRNAs. As expected, in K562 cells, the expression of several of these targets was inverted to that of the miRNA putatively regulating them. Reassuringly, the analysis identified CML as the main disease associated with these miRNAs. MAPK, ErbB, mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF) were the main molecular pathways related with these expression patterns. Utilizing Venn diagrams we found appreciable overlap between the CML-related miRNAs and the signaling pathways-related miRNAs. CONCLUSIONS: The miRNAs identified in this study might offer a pivotal role in CML. Nevertheless, while these data point to a central disease, the precise molecular pathway/s targeted by these miRNAs is variable implying a high level of complexity of miRNA target selection and regulation. These deregulated miRNAs highlight new candidate gene targets allowing for a better understanding of the molecular mechanism underlying the development of CML, and propose possible new avenues for therapeutic treatment. |
format | Online Article Text |
id | pubmed-3325224 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33252242012-04-17 Downregulation of Mir-31, Mir-155, and Mir-564 in Chronic Myeloid Leukemia Cells Hershkovitz Rokah, Oshrat Granot, Galit Ovcharenko, Adelina Modai, Shira Pasmanik-Chor, Metsada Toren, Amos Shomron, Noam Shpilberg, Ofer PLoS One Research Article BACKGROUND/AIMS: MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression and play an important role in cancer development and progression. However, little is known about the role of miRNAs in chronic myeloid leukemia (CML). Our objective is to decipher a miRNA expression signature associated with CML and to determine potential target genes and signaling pathways affected by these signature miRNAs. RESULTS: Using miRNA microarrays and miRNA real-time PCR we characterized the miRNAs expression profile of CML cell lines and patients in reference to non-CML cell lines and healthy blood. Of all miRNAs tested, miR-31, miR-155, and miR-564 were down-regulated in CML cells. Down-regulation of these miRNAs was dependent on BCR-ABL activity. We next analyzed predicted targets and affected pathways of the deregulated miRNAs. As expected, in K562 cells, the expression of several of these targets was inverted to that of the miRNA putatively regulating them. Reassuringly, the analysis identified CML as the main disease associated with these miRNAs. MAPK, ErbB, mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF) were the main molecular pathways related with these expression patterns. Utilizing Venn diagrams we found appreciable overlap between the CML-related miRNAs and the signaling pathways-related miRNAs. CONCLUSIONS: The miRNAs identified in this study might offer a pivotal role in CML. Nevertheless, while these data point to a central disease, the precise molecular pathway/s targeted by these miRNAs is variable implying a high level of complexity of miRNA target selection and regulation. These deregulated miRNAs highlight new candidate gene targets allowing for a better understanding of the molecular mechanism underlying the development of CML, and propose possible new avenues for therapeutic treatment. Public Library of Science 2012-04-12 /pmc/articles/PMC3325224/ /pubmed/22511990 http://dx.doi.org/10.1371/journal.pone.0035501 Text en Hershkovitz Rokah et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hershkovitz Rokah, Oshrat Granot, Galit Ovcharenko, Adelina Modai, Shira Pasmanik-Chor, Metsada Toren, Amos Shomron, Noam Shpilberg, Ofer Downregulation of Mir-31, Mir-155, and Mir-564 in Chronic Myeloid Leukemia Cells |
title | Downregulation of Mir-31, Mir-155, and Mir-564 in Chronic Myeloid Leukemia Cells |
title_full | Downregulation of Mir-31, Mir-155, and Mir-564 in Chronic Myeloid Leukemia Cells |
title_fullStr | Downregulation of Mir-31, Mir-155, and Mir-564 in Chronic Myeloid Leukemia Cells |
title_full_unstemmed | Downregulation of Mir-31, Mir-155, and Mir-564 in Chronic Myeloid Leukemia Cells |
title_short | Downregulation of Mir-31, Mir-155, and Mir-564 in Chronic Myeloid Leukemia Cells |
title_sort | downregulation of mir-31, mir-155, and mir-564 in chronic myeloid leukemia cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325224/ https://www.ncbi.nlm.nih.gov/pubmed/22511990 http://dx.doi.org/10.1371/journal.pone.0035501 |
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