MicroRNA-221 mediates the effects of PDGF-BB on migration, proliferation, and the epithelial-mesenchymal transition in pancreatic cancer cells

The platelet-derived growth factor (PDGF) signaling pathway has been found to play important roles in the development and progression of human cancers by regulating the processes of cell proliferation, apoptosis, migration, invasion, metastasis, and the acquisition of the epithelial-mesenchymal tran...

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Bibliographic Details
Published in:PloS one 2013-08, Vol.8 (8), p.e71309
Main Authors: Su, Anping, He, Sirong, Tian, Bole, Hu, Weiming, Zhang, Zhaoda
Format: Article
Language:English
Subjects:
Analysis
Apoptosis
Biology
Cancer
Cancer cells
Cancer treatment
Cell adhesion & migration
Cell cycle
Cell growth
Cell Line, Tumor
Cell migration
Cell Movement - genetics
Cell proliferation
Cell Proliferation - drug effects
Cyclin-dependent kinase inhibitor p27
Cyclin-Dependent Kinase Inhibitor p27 - genetics
Cyclin-Dependent Kinase Inhibitor p27 - metabolism
Development and progression
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Epithelial-Mesenchymal Transition - drug effects
Epithelial-Mesenchymal Transition - genetics
Gene Expression Regulation, Neoplastic - drug effects
Genotype & phenotype
Humans
Immunoglobulins
Kinases
Liver cancer
Medicine
Mesenchyme
Metastases
Metastasis
MicroRNA
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Pancreatic cancer
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - metabolism
Phenotype
Platelet-derived growth factor
Platelet-derived growth factor BB
Prostate
Proto-Oncogene Proteins c-sis - metabolism
Proto-Oncogene Proteins c-sis - pharmacology
Ribonucleic acid
RNA
RNA Interference
Signal Transduction
Signaling
Stem cells
Studies
Surgery
Thyroid gland
Transcription Factors - genetics
Transcription Factors - metabolism
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Description
Summary:The platelet-derived growth factor (PDGF) signaling pathway has been found to play important roles in the development and progression of human cancers by regulating the processes of cell proliferation, apoptosis, migration, invasion, metastasis, and the acquisition of the epithelial-mesenchymal transition (EMT) phenotype. Moreover, PDGF signaling has also been found to alter the expression profile of miRNAs, leading to the reversal of EMT phenotype. Although the role of miRNAs in cancer has been documented, there are very few studies documenting the cellular consequences of targeted re-expression of specific miRNAs. Therefore, we investigated whether the treatment of human pancreatic cancer cells with PDGF could alter the expression profile of miRNAs, and we also assessed the cellular consequences. Our study demonstrates that miR-221 is essential for the PDGF-mediated EMT phenotype, migration, and growth of pancreatic cancer cells. Down-regulation of TRPS1 by miR-221 is critical for PDGF-mediated acquisition of the EMT phenotype. Additionally, the PDGF-dependent increase in cell proliferation appears to be mediated by inhibition of a specific target of miR-221 and down-regulation of p27Kip1.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0071309