| miR-34a induces the down-regulation of both E2F1 and B-Myb oncogenes in leukemic cells. | |
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MedLine Citation:
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PMID: 21367750 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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PURPOSE: To elucidate new molecular mechanisms able to down-regulated the mRNA levels of key oncogenes, such as B-Myb and E2F1, in a therapeutic perspective. EXPERIMENTAL DESIGN: B-Myb and E2F1 mRNA levels were evaluated in primary B chronic lymphocytic leukemia (B-CLL, n=10), acute myeloid leukemia (AML, n=5) patient cells, in a variety of p53wild-type and p53mutated/deleted leukemic cell lines, as well as in primary endothelial cells and fibroblasts. Knock-down experiments with siRNA for p53 and E2F1 and overexpression experiments with miR34a were performed to elucidate the role of these pathways in promoting B-Myb down-regulation.RESULTS: In vitro exposure to Nutlin-3, a non-genotoxic activator of p53, variably down-regulated the expression of B-Myb in primary leukemic cells, in p53wild-type myeloid (OCI, MOLM) and lymphoblastoid (SKW6.4, EHEB) but not in p53mutated (NB4, BJAB, MAVER) or p53deleted (HL-60) leukemic cell lines. The transcriptional repression of B-Myb was observed also in primary normal endothelial cells and fibroblasts. B-Myb down-regulation played a critical role in the cell cycle block in G1 phase induced by Nutlin-3, as demonstrated by transfection experiments with specific siRNA. Moreover, we have provided experimental evidence suggesting that miR-34a is a central mediator in the repression of B-Myb both directly and through E2F1. CONCLUSIONS: Due to the role of B-Myb and E2F1 transcription factors in controlling cell cycle progression of leukemic cells, the down-regulation of these oncogenes by miR-34a suggests the usefulness of therapeutic approaches aimed to modulate the levels of miR-34a. |
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Authors:
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Giorgio Zauli; Rebecca Voltan; Maria Grazia di Iasio; Raffaella Bosco; Elisabetta Melloni; Maria Elena Sana; Paola Secchiero |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-2 |
Journal Detail:
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Title: Clinical cancer research : an official journal of the American Association for Cancer Research Volume: - ISSN: 1078-0432 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9502500 Medline TA: Clin Cancer Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Morphology and Embryology, University of Ferrara. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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