RESUMO
In the present study we have applied the siRNA approach for substantial reduction of AML1-ETO and RUNX1 (K83N) expression, which are frequently found in the leukemic cells. We have designed small hairpin RNAs (shRNA) for targeting AML1-ETO oncogene and a region close to the 5'-untranslated region of mRNA for the mutant RUNX1 (K83N) oncogene and expressed the shRNAs in lentiviral vectors. We report a stable reduction in expression of the oncogenes following the introduction of shRNAs into cells.
Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/biossíntese , Regulação para Baixo , Regulação Leucêmica da Expressão Gênica , Leucemia/metabolismo , Mutação de Sentido Incorreto , Proteínas de Fusão Oncogênica/biossíntese , Interferência de RNA , Regiões 5' não Traduzidas/genética , Substituição de Aminoácidos , Animais , Linhagem Celular Tumoral , Subunidade alfa 2 de Fator de Ligação ao Core/antagonistas & inibidores , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Células HEK293 , Humanos , Leucemia/genética , Camundongos , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Proteínas de Fusão Oncogênica/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Proteína 1 Parceira de Translocação de RUNX1RESUMO
Acute myeloid leukemia (AML) is a malignant blood disease caused by different mutations that enhance the proliferative activity and survival of blood cells and affect their differentiation and apoptosis. The most frequent disorders in AML are translocations between chromosomes 21 and 8 leading to production of a chimeric oncogene, AML1-ETO, and hyperexpression of the receptor tyrosine kinase KIT. Mutations in these genes often occur jointly. The presence in cells of two activated oncogenes is likely to trigger their malignization. The current approaches for treatment of oncologic diseases (bone marrow transplantation, radiotherapy, and chemotherapy) have significant shortcomings, and thus many laboratories are intensively developing new approaches against leukemias. Inhibiting expression of activated leukemic oncogenes based on the principle of RNA interference seems to be a promising approach in this field.