S100P/RAGE signaling regulates microRNA-155 expression via AP-1 activation in colon cancer
| Autor: | Benjamin C. Onyeagucha, Erik K. Flemington, Melania E. Mercado-Pimentel, Mark A. Nelson, Jennifer Hutchison |
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| Rok vydání: | 2013 |
| Předmět: |
Transcriptional Activation
Colorectal cancer Receptor for Advanced Glycation End Products Motility Stimulation Biology Models Biological Article miR-155 microRNA Tumor Cells Cultured medicine Humans Receptors Immunologic Receptor Gene knockdown Activator (genetics) Calcium-Binding Proteins Cell Biology medicine.disease Molecular biology Neoplasm Proteins Gene Expression Regulation Neoplastic Transcription Factor AP-1 MicroRNAs HEK293 Cells Gene Knockdown Techniques Colonic Neoplasms Cancer research Signal Transduction |
| Zdroj: | Experimental Cell Research. 319:2081-2090 |
| ISSN: | 0014-4827 |
| Popis: | Accumulating evidence indicates that elevated S100P promotes the pathogenesis of cancers, including colon cancer. S100P exerts its effects by binding to and activating the Receptor for Advance Glycation End-products (RAGE). The effects of up-regulated S100P/RAGE signaling on cell functions are well documented. Despite these observations, little is known about the downstream targets of S100P/RAGE signaling. In the present study, we demonstrated for the first time that activation of RAGE by S100P regulates oncogenic microRNA-155 (miR-155) expression through Activator Protein-1 (AP-1) stimulation in colon cancer cells. Ectopic S100P up-regulated miR-155 levels in human colon cancer cells. Conversely, knockdown of S100P resulted in a decrease in miR-155 levels. Exogenous S100P induced miR-155 expression, but blockage of the RAGE with anti-RAGE antibody suppressed the induction of miR-155 by exogenous S100P. Attenuation of AP-1 activation through pharmacological inhibition of MEK activation or genetic inhibition of c-Jun activation using dominant negative c-Jun (TAM67) suppressed miR-155 induction by exogenous S100P. Also, S100P treatment stimulated the enrichment of c-Fos, an AP-1 family member, at the miR-155 host gene promoter site. Finally, a functional study demonstrated that miR-155 knockdown decreases colon cancer cell growth, motility, and invasion. Altogether, these data demonstrate that the expression of miR-155 is regulated by S100P and is dependent on RAGE activation and stimulation of AP-1. |
| Databáze: | OpenAIRE |
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