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An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation
- Source :
- Metastasis Genes and Functions, Barcellona, 2008, info:cnr-pdr/source/autori:Francesco Talotta, Amelia Cimmino, Maria Rosaria Matarazzo, Laura Casalino, Gabriella De Vita, Maurizio DEsposito, Roberto Di Lauro and Pasquale Verde/congresso_nome:Metastasis Genes and Functions/congresso_luogo:Barcellona/congresso_data:2008/anno:2008/pagina_da:/pagina_a:/intervallo_pagine, Oncogene (Basingstoke) 28 (2009): 73–84. doi:10.1038/onc.2008.370, info:cnr-pdr/source/autori:Talotta F.; Cimmino A.; Matarazzo M.R.; Casalino L.; De Vita G.; D'Esposito M.; Di Lauro R.; Verde P./titolo:An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation/doi:10.1038%2Fonc.2008.370/rivista:Oncogene (Basingstoke)/anno:2009/pagina_da:73/pagina_a:84/intervallo_pagine:73–84/volume:28
- Publication Year :
- 2008
-
Abstract
- The transcription factor AP-1 plays key roles in tumorigenesis, by regulating a variety of protein-coding genes, implicated in multiple hallmarks of cancer. Among non-coding genes, no AP-1 target has been described yet in tumorigenesis. MicroRNAs (miRNAs) are negative post-transcriptional regulators of protein-coding genes. miRNA expression signatures are highly relevant in cancer and several tumor-associated miRNAs (oncomirs) play critical roles in oncogenesis. Here, we show that the miRNA miR-21, which represents the most frequently upregulated oncomir in solid tumors, is induced by AP-1 in response to RAS. By analyzing validated miR-21 targets, we have found that the tumor suppressors PTEN and PDCD4 are downregulated by RAS in an AP-1- and miR-21-dependent fashion. We further show that, given the role of PDCD4 as negative regulator of AP-1, the miR-21-mediated downregulation of PDCD4 is essential for the maximal induction of AP-1 activity in response to RAS. Our data reveal a novel mechanism of positive autoregulation of the AP-1 complex in RAS transformation and disclose the function of oncomirs as critical targets and regulators of AP-1 in tumorigenesis.
- Subjects :
- PTEN
Cancer Research
C-JUN
Tumor suppressor gene
Cell Survival
Proto-Oncogene Proteins c-jun
Thyroid Gland
medicine.disease_cause
Downregulation and upregulation
Cell Line, Tumor
microRNA
MICRORNA-21 TARGETS
TUMORIGENESIS
Genetics
medicine
BREAST-CANCER
Gene silencing
Animals
Homeostasis
Humans
TUMOR-SUPPRESSOR PDCD4
MESSENGER-RNAS
Molecular Biology
Transcription factor
GENE-EXPRESSION
PDCD4
biology
PTEN Phosphohydrolase
Oncomir
ONCOGENIC RAS
AP-1
Rats
Transcription Factor AP-1
TRANSCRIPTION FACTORS
MicroRNAs
Cell Transformation, Neoplastic
CELLS
Cancer research
biology.protein
ras Proteins
miR-21
Carcinogenesis
Apoptosis Regulatory Proteins
Proto-Oncogene Proteins c-fos
RAS
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Metastasis Genes and Functions, Barcellona, 2008, info:cnr-pdr/source/autori:Francesco Talotta, Amelia Cimmino, Maria Rosaria Matarazzo, Laura Casalino, Gabriella De Vita, Maurizio DEsposito, Roberto Di Lauro and Pasquale Verde/congresso_nome:Metastasis Genes and Functions/congresso_luogo:Barcellona/congresso_data:2008/anno:2008/pagina_da:/pagina_a:/intervallo_pagine, Oncogene (Basingstoke) 28 (2009): 73–84. doi:10.1038/onc.2008.370, info:cnr-pdr/source/autori:Talotta F.; Cimmino A.; Matarazzo M.R.; Casalino L.; De Vita G.; D'Esposito M.; Di Lauro R.; Verde P./titolo:An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation/doi:10.1038%2Fonc.2008.370/rivista:Oncogene (Basingstoke)/anno:2009/pagina_da:73/pagina_a:84/intervallo_pagine:73–84/volume:28
- Accession number :
- edsair.doi.dedup.....1287de50956fec9801fea50359fd0b6e