| Journal: | Archivos venezolanos de farmacología y terapéutica |
| Database: | PERIÓDICA |
| System number: | 000317231 |
| ISSN: | 0798-0264 |
| Authors: | Wynter, Coral1 Alfonzo, Marcelo Lippo de Becemberg, Itala |
| Institutions: | 1Universidad Central de Venezuela, Instituto de Medicina Experimental, Caracas, Distrito Federal. Venezuela |
| Year: | 2008 |
| Volumen: | 27 |
| Number: | 1 |
| Pages: | 14-18 |
| Country: | Venezuela |
| Language: | Inglés |
| Document type: | Artículo |
| Approach: | Experimental, aplicado |
| English abstract | The recent discoveries of the RNA-mediated interference system in cells could explain all of the known features of human carcinogenesis. A novel idea, proposed here, is that the cell has the ability to recognize a mutated protein and/or mRNA. Secondly, the cell can generate its own short interfering RNA (siRNA) using an RNA polymerase to destroy mutated mRNA, even when only a single base pair in the gene has mutated. The anti-sense strand of the short RNA molecule (called sicRNA), targets the mutated mRNA of an oncogene or a tumour suppressor. During cell mitosis, the sicRNA complex can move into the nucleus to target the mutated gene. The sicRNA triggers the assembly of protein complexes leading to epigenetic modification of the promoter site of the mutant gene. In some instances, instead of methylation, the homologous DNA is degraded, leading to loss of heterozygosity. The factors controlling these two actions are unknown but the result is gene silencing or physical destruction of the mutant gene. An error in RNAi defence occurs when the sicRNA during methylation of the target gene, inadvertently interferes with the production of a miRNA specific for that tissue. This produces a change in the profile of correct proteins for that tissue. On a rare occasion, a preneoplastic stem cell will survive if miRNA interference switches on/off a gene involved in apoptosis, as well as a gene involved in cell proliferation and DNA damage surveillance. The driving force of carcinogenesis is the sequential loss of specific miRNAs |
| Disciplines: | Medicina, Química |
| Keyword: | Oncología, Bioquímica, Genética, Carcinogénesis, Regulación génica, ARN, Metilación, Interferencia genética |
| Keyword: | Medicine, Chemistry, Oncology, Biochemistry, Carcinogenesis, Gene regulation, RNA, Methylation, Genetic interference, Genetics |
| Full text: | Texto completo (Ver HTML) |
