Antitumor activity induced by regulatory RNA: possible role of RNA-dependent protein kinase and nuclear factor-κB
| Autor: | Liliana R. de Souza, Fernando Luiz De Lucca, Maria Angelica E. Watanabe, Joana M. Murad |
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| Rok vydání: | 2003 |
| Předmět: |
RNA
Untranslated Polyadenylation Guinea Pigs Melanoma Experimental chemical and pharmacologic phenomena Biology Immunotherapy Adoptive Fas ligand Mice eIF-2 Kinase Gene expression Animals Lymphocytes Neoplasm Metastasis Protein kinase A neoplasms Transcription factor Pharmacology EIF-2 kinase NF-kappa B RNA hemic and immune systems Molecular biology Protein kinase R respiratory tract diseases Cell biology Mice Inbred C57BL biology.protein biological phenomena cell phenomena and immunity Neoplasm Transplantation |
| Zdroj: | European Journal of Pharmacology. 465:205-210 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/s0014-2999(03)01480-8 |
| Popis: | Regulatory RNAs are noncoding RNAs that can regulate gene expression. Our previous results showed that regulatory RNAs can induce the production of interleukin-1, interleukin-2, interleukin-8, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, and Fas ligand (FasL). These cytokines and FasL are involved in host defense mechanisms against tumors. B16-F10 melanoma cells are highly metastatic to the lungs and we showed that lymphocytes treated with the regulatory B16-RNA reduce significantly the number of metastatic nodules. We also found that B16-RNA activates RNA-dependent protein kinase (PKR) and the active B16-RNA fraction is polyadenylated with a sedimentation coefficient of 18S. Our findings suggest that the antitumor activity of B16-RNA is mediated by PKR through activation of the transcription factor NF-kappaB. Thus, B16-RNA may act as a regulatory RNA and may regulate gene expression at transcriptional level. This study provides the rationale for the use of B16-RNA as an immunomodulator in melanoma. |
| Databáze: | OpenAIRE |
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