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Down-regulation of specific miRNAs enhances the expression of the gene Smoothened and contributes to T-cell lymphoblastic lymphoma development.

Inappropriate activation of the GLI/hedgehog (GLI/Hh) signalling occurs in several human cancers, including haematological neoplasms. However, little is known about its relevance in precursor T-cell lymphoblastic lymphomas (T-LBL) development. Moreover, the mechanisms whereby GLI/Hh signalling is ac... Full description

Journal Title: Carcinogenesis April 2013, Vol.34(4), pp.902-908
Main Author: González-Gugel, Elena
Other Authors: Villa-Morales, María , Santos, Javier , Bueno, Maria José , Malumbres, Marcos , Rodríguez-Pinilla, Socorro María , Piris, Miguel Ángel , Fernández-Piqueras, José
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1460-2180 ; DOI: 10.1093/carcin/bgs404
Link: http://search.proquest.com/docview/1324391681/?pq-origsite=primo
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recordid: proquest1324391681
title: Down-regulation of specific miRNAs enhances the expression of the gene Smoothened and contributes to T-cell lymphoblastic lymphoma development.
format: Article
creator:
  • González-Gugel, Elena
  • Villa-Morales, María
  • Santos, Javier
  • Bueno, Maria José
  • Malumbres, Marcos
  • Rodríguez-Pinilla, Socorro María
  • Piris, Miguel Ángel
  • Fernández-Piqueras, José
subjects:
  • 3t3 Cells–Genetics
  • Animals–Metabolism
  • Cell Line, Tumor–Genetics
  • Cell Proliferation–Metabolism
  • Cell Survival–Genetics
  • Down-Regulation–Genetics
  • Hedgehog Proteins–Genetics
  • Humans–Biosynthesis
  • Jurkat Cells–Genetics
  • Kruppel-Like Transcription Factors–Genetics
  • Lymphoma, T-Cell–Pharmacology
  • Mice–Pharmacology
  • Mice, Inbred C57bl–Pharmacology
  • Micrornas–Pharmacology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma–Pharmacology
  • RNA Interference–Pharmacology
  • RNA, Small Interfering–Pharmacology
  • Receptors, G-Protein-Coupled–Pharmacology
  • Signal Transduction–Pharmacology
  • Smoothened Receptor–Pharmacology
  • Up-Regulation–Pharmacology
  • Veratrum Alkaloids–Pharmacology
  • Zinc Finger Protein Gli1–Pharmacology
  • Gli Protein, Mouse
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors
  • Mirn193 Microrna, Human
  • Micrornas
  • Mirn141 Microrna, Mouse
  • Mirn30d Microrna, Mouse
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled
  • Smo Protein, Mouse
  • Smoothened Receptor
  • Veratrum Alkaloids
  • Zinc Finger Protein Gli1
  • Cyclopamine
ispartof: Carcinogenesis, April 2013, Vol.34(4), pp.902-908
description: Inappropriate activation of the GLI/hedgehog (GLI/Hh) signalling occurs in several human cancers, including haematological neoplasms. However, little is known about its relevance in precursor T-cell lymphoblastic lymphomas (T-LBL) development. Moreover, the mechanisms whereby GLI/Hh signalling is activated in haematological malignancies are not fully clear. Here, we show that the gene Smoothened (SMO), the only non-redundant gene of this pathway, is up-regulated in mouse and human T-LBL. Interestingly, down-regulation of micro-RNAs mmu-miR-30a and mmu-miR-141 as well as hsa-miR-193b clearly contributes to enhance the expression of this gene in mouse and human lymphomas and, subsequently, to activate the GLI/Hh signalling. Activation of the GLI/Hh signalling in T-LBL promotes cell survival and proliferation, since inhibition of the pathway using short-hairpin-RNA-mediated SMO knockdown, or cyclopamine as a specific antagonist, significantly reduces these cellular processes. These findings suggest that sustained SMO up-regulation may contribute to T-LBL development and advocate the use of specific SMO inhibitors or microRNAs-based therapies as an attractive possibility to treat an important subset of T-LBL.
language: eng
source:
identifier: E-ISSN: 1460-2180 ; DOI: 10.1093/carcin/bgs404
fulltext: fulltext
issn:
  • 14602180
  • 1460-2180
url: Link


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titleDown-regulation of specific miRNAs enhances the expression of the gene Smoothened and contributes to T-cell lymphoblastic lymphoma development.
creatorGonzález-Gugel, Elena ; Villa-Morales, María ; Santos, Javier ; Bueno, Maria José ; Malumbres, Marcos ; Rodríguez-Pinilla, Socorro María ; Piris, Miguel Ángel ; Fernández-Piqueras, José
contributorGonzález-Gugel, Elena (correspondence author) ; González-Gugel, Elena (record owner)
ispartofCarcinogenesis, April 2013, Vol.34(4), pp.902-908
identifierE-ISSN: 1460-2180 ; DOI: 10.1093/carcin/bgs404
subject3t3 Cells–Genetics ; Animals–Metabolism ; Cell Line, Tumor–Genetics ; Cell Proliferation–Metabolism ; Cell Survival–Genetics ; Down-Regulation–Genetics ; Hedgehog Proteins–Genetics ; Humans–Biosynthesis ; Jurkat Cells–Genetics ; Kruppel-Like Transcription Factors–Genetics ; Lymphoma, T-Cell–Pharmacology ; Mice–Pharmacology ; Mice, Inbred C57bl–Pharmacology ; Micrornas–Pharmacology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma–Pharmacology ; RNA Interference–Pharmacology ; RNA, Small Interfering–Pharmacology ; Receptors, G-Protein-Coupled–Pharmacology ; Signal Transduction–Pharmacology ; Smoothened Receptor–Pharmacology ; Up-Regulation–Pharmacology ; Veratrum Alkaloids–Pharmacology ; Zinc Finger Protein Gli1–Pharmacology ; Gli Protein, Mouse ; Hedgehog Proteins ; Kruppel-Like Transcription Factors ; Mirn193 Microrna, Human ; Micrornas ; Mirn141 Microrna, Mouse ; Mirn30d Microrna, Mouse ; RNA, Small Interfering ; Receptors, G-Protein-Coupled ; Smo Protein, Mouse ; Smoothened Receptor ; Veratrum Alkaloids ; Zinc Finger Protein Gli1 ; Cyclopamine
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descriptionInappropriate activation of the GLI/hedgehog (GLI/Hh) signalling occurs in several human cancers, including haematological neoplasms. However, little is known about its relevance in precursor T-cell lymphoblastic lymphomas (T-LBL) development. Moreover, the mechanisms whereby GLI/Hh signalling is activated in haematological malignancies are not fully clear. Here, we show that the gene Smoothened (SMO), the only non-redundant gene of this pathway, is up-regulated in mouse and human T-LBL. Interestingly, down-regulation of micro-RNAs mmu-miR-30a and mmu-miR-141 as well as hsa-miR-193b clearly contributes to enhance the expression of this gene in mouse and human lymphomas and, subsequently, to activate the GLI/Hh signalling. Activation of the GLI/Hh signalling in T-LBL promotes cell survival and proliferation, since inhibition of the pathway using short-hairpin-RNA-mediated SMO knockdown, or cyclopamine as a specific antagonist, significantly reduces these cellular processes. These findings suggest that sustained SMO up-regulation may contribute to T-LBL development and advocate the use of specific SMO inhibitors or microRNAs-based therapies as an attractive possibility to treat an important subset of T-LBL.
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titleDown-regulation of specific miRNAs enhances the expression of the gene Smoothened and contributes to T-cell lymphoblastic lymphoma development.
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titleDown-regulation of specific miRNAs enhances the expression of the gene Smoothened and contributes to T-cell lymphoblastic lymphoma development.
authorGonzález-Gugel, Elena ; Villa-Morales, María ; Santos, Javier ; Bueno, Maria José ; Malumbres, Marcos ; Rodríguez-Pinilla, Socorro María ; Piris, Miguel Ángel ; Fernández-Piqueras, José
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03t3 Cells–Genetics
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6Hedgehog Proteins–Genetics
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