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Down-regulation of specific miRNAs enhances the expression of the gene Smoothened and contributes to T-cell lymphoblastic lymphoma development
- Source :
- Carcinogenesis. 34:902-908
- Publication Year :
- 2013
- Publisher :
- Oxford University Press (OUP), 2013.
-
Abstract
- 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.
- Subjects :
- Cancer Research
Cyclopamine
Cell Survival
Kruppel-Like Transcription Factors
Down-Regulation
Biology
Lymphoma, T-Cell
Zinc Finger Protein GLI1
Jurkat cells
Receptors, G-Protein-Coupled
Jurkat Cells
Mice
chemistry.chemical_compound
RNA interference
Cell Line, Tumor
microRNA
Animals
Humans
Hedgehog Proteins
RNA, Small Interfering
Hedgehog
Cell Proliferation
Gene knockdown
Veratrum Alkaloids
3T3 Cells
General Medicine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Smoothened Receptor
Up-Regulation
Mice, Inbred C57BL
MicroRNAs
chemistry
Cancer research
RNA Interference
Smoothened
Signal Transduction
Subjects
Details
- ISSN :
- 14602180 and 01433334
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Carcinogenesis
- Accession number :
- edsair.doi.dedup.....ec153f3c1dae38a56ab7308c2876453c