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p53 regulates epithelial–mesenchymal transition through microRNAs targeting ZEB1 and ZEB2
- Source :
- Journal of Experimental Medicine, Journal of Experimental Medicine, 2011, 208 (5), pp.875-883. ⟨10.1084/jem.20110235⟩, Journal of Experimental Medicine, Rockefeller University Press, 2011, 208 (5), pp.875-883. ⟨10.1084/jem.20110235⟩, The Journal of Experimental Medicine
- Publication Year :
- 2011
- Publisher :
- HAL CCSD, 2011.
-
Abstract
- By transactivating expression of miRNAs that repress expression of the ZEB1 and ZEB2 transcription factors, p53 inhibits the epithelial–mesenchymal transition.<br />p53 suppresses tumor progression and metastasis. Epithelial–mesenchymal transition (EMT) is a key process in tumor progression and metastasis. The transcription factors ZEB1 and ZEB2 promote EMT. Here, we show that p53 suppresses EMT by repressing expression of ZEB1 and ZEB2. By profiling 92 primary hepatocellular carcinomas (HCCs) and 9 HCC cell lines, we found that p53 up-regulates microRNAs (miRNAs), including miR-200 and miR-192 family members. The miR-200 family members transactivated by p53 then repress ZEB1/2 expression. p53-regulated miR-192 family members also repress ZEB2 expression. Inhibition or overexpression of the miRNAs affects p53-regulated EMT by altering ZEB1 and ZEB2 expression. Our findings indicate that p53 can regulate EMT, and that p53-regulated miRNAs are critical mediators of p53-regulated EMT.
- Subjects :
- Male
MESH: Zinc Finger E-box-Binding Homeobox 1
genetics/metabolism
biosynthesis/genetics
Metastasis
genetics/metabolism/pathology
0302 clinical medicine
MESH: Liver Neoplasms
Immunology and Allergy
genetics
RNA, Neoplasm
Neoplasm Metastasis
MESH: Carcinoma, Hepatocellular
MESH: Tumor Suppressor Protein p53
0303 health sciences
digestive, oral, and skin physiology
Liver Neoplasms
Hep G2 Cells
MESH: Gene Expression Regulation, Neoplastic
MESH: Transcription Factors
Gene Expression Regulation, Neoplastic
MESH: Repressor Proteins
030220 oncology & carcinogenesis
embryonic structures
Female
Transcriptional Activation
Carcinoma, Hepatocellular
Epithelial-Mesenchymal Transition
Immunology
Repressor
MESH: Hep G2 Cells
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
03 medical and health sciences
MESH: Gene Expression Profiling
[SDV.CAN] Life Sciences [q-bio]/Cancer
microRNA
MESH: Homeodomain Proteins
medicine
[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Epithelial–mesenchymal transition
Transcription factor
Zinc Finger E-box Binding Homeobox 2
030304 developmental biology
MESH: Zinc Finger E-box Binding Homeobox 2
Homeodomain Proteins
Neoplastic
MESH: Humans
Gene Expression Profiling
Carcinoma
Brief Definitive Report
Zinc Finger E-box-Binding Homeobox 1
Hepatocellular
Cell Biology
HCCS
medicine.disease
MESH: RNA, Neoplasm
MESH: Neoplasm Metastasis
MESH: Male
Repressor Proteins
Gene expression profiling
MicroRNAs
MESH: Epithelial-Mesenchymal Transition
Gene Expression Regulation
Tumor progression
Cancer research
RNA
Neoplasm
MESH: Transcriptional Activation
genetics/metabolism/pathology, Epithelial-Mesenchymal Transition, Female, Gene Expression Profiling, Gene Expression Regulation
Neoplastic, Hep G2 Cells, Homeodomain Proteins
biosynthesis/genetics, Humans, Liver Neoplasms
genetics/metabolism/pathology, Male, MicroRNAs
genetics/metabolism, Neoplasm Metastasis, RNA
genetics/metabolism, Repressor Proteins
biosynthesis/genetics, Transcription Factors
biosynthesis/genetics, Transcriptional Activation
genetics, Tumor Suppressor Protein p53
Tumor Suppressor Protein p53
MESH: Female
MESH: MicroRNAs
030215 immunology
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 00221007 and 15409538
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine, Journal of Experimental Medicine, 2011, 208 (5), pp.875-883. ⟨10.1084/jem.20110235⟩, Journal of Experimental Medicine, Rockefeller University Press, 2011, 208 (5), pp.875-883. ⟨10.1084/jem.20110235⟩, The Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....e8be3134e71e2530e86721af92da340f