Author
Catherine Labbaye
Other affiliations: University of Rome Tor Vergata
Bio: Catherine Labbaye is an academic researcher from Istituto Superiore di Sanità. The author has contributed to research in topics: Haematopoiesis & Leukemia. The author has an hindex of 17, co-authored 27 publications receiving 2098 citations. Previous affiliations of Catherine Labbaye include University of Rome Tor Vergata.
Papers
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TL;DR: It is proposed thatmiR-15a and miR-16 act as tumor suppressor genes in prostate cancer through the control of cell survival, proliferation and invasion through the regulation of BCL2 and CCND1.
Abstract: Two microRNAs, miR-15a and miR-16, localize to a chromosome region that is frequently deleted in cancer. Bonci et al. now show that these microRNAs have tumor suppressive effects in prostate cancer cells and regulate the expression of crucial oncogenic targets.
966 citations
TL;DR: The data indicate that megakaryopoiesis is controlled by a cascade pathway, in which PLZF suppresses miR-146a transcription and thereby activates CXCR4 translation.
Abstract: MicroRNAs (miRNAs or miRs) regulate diverse normal and abnormal cell functions. We have identified a regulatory pathway in normal megakaryopoiesis, involving the PLZF transcription factor, miR-146a and the SDF-1 receptor CXCR4. In leukaemic cell lines PLZF overexpression downmodulated miR-146a and upregulated CXCR4 protein, whereas PLZF knockdown induced the opposite effects. In vitro assays showed that PLZF interacts with and inhibits the miR-146a promoter, and that miR-146a targets CXCR4 mRNA, impeding its translation. In megakaryopoietic cultures of CD34(+) progenitors, PLZF was upregulated, whereas miR-146a expression decreased and CXCR4 protein increased. MiR-146a overexpression and PLZF or CXCR4 silencing impaired megakaryocytic (Mk) proliferation, differentiation and maturation, as well as Mk colony formation. Mir-146a knockdown induced the opposite effects. Rescue experiments indicated that the effects of PLZF and miR-146a are mediated by miR-146a and CXCR4, respectively. Our data indicate that megakaryopoiesis is controlled by a cascade pathway, in which PLZF suppresses miR-146a transcription and thereby activates CXCR4 translation.
231 citations
TL;DR: This review focuses on recent progress in analyzing the functional role of miR-146a in the control of normal and malignant hematopoiesis and gene knockout studies indicate a role for this miRNA as a tumor suppressor.
Abstract: MicroRNA (miRs) represent a class of small non-coding regulatory RNAs playing a major role in the control of gene expression by repressing protein synthesis at the post-transcriptional level. Studies carried out during the last years have shown that some miRNAs plays a key role in the control of normal and malignant hgematopoiesis. In this review we focus on recent progress in analyzing the functional role of miR-146a in the control of normal and malignant hematopoiesis. On the other hand, this miRNA has shown to impact in the control of innate immune responses. Finally, many recent studies indicate a deregulation of miR-146 in many solid tumors and gene knockout studies indicate a role for this miRNA as a tumor suppressor.
200 citations
TL;DR: The demonstration that miR-155 overexpression plays a key pathogenic role in some lymphomas and acute myeloid leukemias has led to the development of an antagomir-based approach as a new promising therapeutic strategy.
Abstract: MicroRNAs (miRNAs or miRs) are a class of evolutionarily-conserved small, regulatory non-coding RNAs, 19–3 nucleotides in length, that negatively regulate protein coding gene transcripts’ expression. miR-146 (146a and 146b) and miR-155 are among the first and most studied miRs for their multiple roles in the control of the innate and adaptive immune processes and for their deregulation and oncogenic role in some tumors. In the present review, we have focused on the recent acquisitions about the key role played by miR-146a, miR-146b and miR-155 in the control of the immune system and in myeloid tumorigenesis. Growing experimental evidence indicates an opposite role of miR-146a with respect to miR-155 in the fine regulation of many steps of the immune response, acting at the level of the various cell types involved in innate and adaptive immune mechanisms. The demonstration that miR-155 overexpression plays a key pathogenic role in some lymphomas and acute myeloid leukemias has led to the development of an antagomir-based approach as a new promising therapeutic strategy.
159 citations
TL;DR: The results indicate the expression and key role of GATA-2 in the early stages of HPC proliferation/differentiation and NF-E2 and Gata-1 expression and function are apparently restricted to erythroid differentiation and maturation.
Abstract: We have explored the expression of the transcription factors GATA-1, GATA-2, and NF-E2 in purified early hematopoietic progenitor cells (HPCs) induced to gradual unilineage erythroid or granulocytic differentiation by growth factor stimulus. GATA-2 mRNA and protein, already expressed in quiescent HPCs, is rapidly induced as early as 3 h after growth factor stimulus, but then declines in advanced erythroid and granulocytic differentiation and maturation. NF-E2 and GATA-1 mRNAs and proteins, though not detected in quiescent HPCs, are gradually induced at 24-48 h in both erythroid and granulocytic culture. Beginning at late differentiation/early maturation stage, both transcription factors are further accumulated in the erythroid pathway, whereas they are suppressed in the granulopoietic series. Similarly, the erythropoietin receptor (EpR) is induced and sustainedly expressed during erythroid differentiation, although beginning at later times (i.e., day 5), whereas it is barely expressed in the granulopoietic pathway. In the first series of functional studies, HPCs were treated with antisense oligomers targeted to transcription factor mRNA: inhibition of GATA-2 expression caused a decreased number of both erythroid and granulocyte-monocytic clones, whereas inhibition of NF-E2 or GATA-1 expression induced a selective impairment of erythroid colony formation. In a second series of functional studies, HPCs treated with retinoic acid were induced to shift from erythroid to granulocytic differentiation (Labbaye et al. 1994. Blood. 83:651-656); this was coupled with abrogation of GATA-1, NF-E2, and EpR expression and conversely enhanced GATA-2 levels. These results indicate the expression and key role of GATA-2 in the early stages of HPC proliferation/differentiation. Conversely, NF-E2 and GATA-1 expression and function are apparently restricted to erythroid differentiation and maturation: their expression precedes that of the EpR, and their function may be in part mediated via the EpR.
120 citations
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TL;DR: Because malignant cells show dependence on the dysregulated expression of miRNA genes, which in turn control or are controlled by the dysregulation of multiple protein-coding oncogenes or tumour suppressor genes, these small RNAs provide important opportunities for the development of future miRNA-based therapies.
Abstract: Over the past several years it has become clear that alterations in the expression of microRNA (miRNA) genes contribute to the pathogenesis of most — if not all — human malignancies. These alterations can be caused by various mechanisms, including deletions, amplifications or mutations involving miRNA loci, epigenetic silencing or the dysregulation of transcription factors that target specific miRNAs. Because malignant cells show dependence on the dysregulated expression of miRNA genes, which in turn control or are controlled by the dysregulation of multiple protein-coding oncogenes or tumour suppressor genes, these small RNAs provide important opportunities for the development of future miRNA-based therapies.
2,873 citations
TL;DR: It is shown that miRNAs are released through a ceramide-dependent secretory machinery and that the secretory miRNAAs are transferable and functional in the recipient cells and that a tumor-suppressive miRNA secreted via this pathway was transported between cells and exerted gene silencing in the recipients cells, thereby leading to cell growth inhibition.
1,751 citations
TL;DR: The role of miRNAAs in tumorigenesis is described and the rationale, the strategies and the challenges for the therapeutic targeting of miRNAs in cancer are critically discussed.
Abstract: MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that regulate gene expression. Early studies have shown that miRNA expression is deregulated in cancer and experimental data indicate that cancer phenotypes can be modified by targeting miRNA expression. Based on these observations, miRNA-based anticancer therapies are being developed, either alone or in combination with current targeted therapies, with the goal to improve disease response and increase cure rates. The advantage of using miRNA approaches is based on its ability to concurrently target multiple effectors of pathways involved in cell differentiation, proliferation and survival. In this Review, we describe the role of miRNAs in tumorigenesis and critically discuss the rationale, the strategies and the challenges for the therapeutic targeting of miRNAs in cancer.
1,399 citations
TL;DR: POLYMORPHONUCLEAR leukocytes were discovered by Paul Ehrlich when fixation and staining techniques made it possible to identify the lobulated nucleus and the granules that have given name to these cells and allowed for their classification as eosinophil, basophils, and neutrophils.
1,351 citations
TL;DR: The ability of cyclin D1 to activate the cyclin-dependent kinases CDK4 and CDK6 is the most extensively documented mechanism for their oncogenic actions and provides an attractive therapeutic target.
Abstract: Cyclin D1, and to a lesser extent the other D-type cyclins, is frequently deregulated in cancer and is a biomarker of cancer phenotype and disease progression. The ability of these cyclins to activate the cyclin-dependent kinases (CDKs) CDK4 and CDK6 is the most extensively documented mechanism for their oncogenic actions and provides an attractive therapeutic target. Is this an effective means of targeting the cyclin D oncogenes, and how might the patient subgroups that are most likely to benefit be identified?
1,168 citations