RESUMO

RNAi (RNA interference) is a natural process by which eukaryotic cells silence gene expression through small interference RNAs (siRNA) which are complementary to messenger RNA (mRNA). In this process, the siRNA that are 21-25 nucleotides long and are known as microRNA (miRNA), either associate with the RNA-induced silencing complex (RISC), which targets and cleaves the complementary mRNAs by the endonucleolytic pathway, or repress the translation. It is also possible to silence exogenous gene expression during viral infections by using DNA templates to transcribe siRNA with properties that are identical to those of bioactive microRNA. Persistent human papillomavirus (HPV) infection is the main etiological agent during cervical cancer development and the HPV E6 and E7 oncogenes, which induce cellular transformation and immortalization, represent strategic targets to be silenced with siRNA. In several in vitro and in vivo studies, it has been demonstrated that the introduction of siRNA directed against the E6 and E7 oncogenes in human tumoral cervical cells transformed by HPV, leads to the efficient silencing of HPV E6 and E7 oncogene expression, which induces the accumulation of the products of the p53 and pRb tumor suppressor genes and activates the mechanism of programmed cell death by apoptosis; thus, the progression of the tumoral growth process may be prevented. The goal of this review is to analyze the microRNA biogenesis process in the silencing of gene expression and to discuss the different protocols for the use of siRNA as a potential gene therapy strategy for the treatment of cervical cancer.

Assuntos

Regulação Neoplásica da Expressão Gênica/genética , Terapia Genética/métodos , MicroRNAs/genética , Interferência de RNA , RNA Mensageiro/genética , RNA Neoplásico/genética , Neoplasias do Colo do Útero/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Transformação Celular Viral , Terapia Combinada , Desenho de Fármacos , Feminino , Gammapapillomavirus/genética , Gammapapillomavirus/patogenicidade , Gammapapillomavirus/fisiologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Viral da Expressão Gênica/genética , Humanos , MicroRNAs/biossíntese , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/fisiologia , Oncogenes , Infecções por Papillomavirus/genética , Biossíntese de Proteínas , RNA Mensageiro/antagonistas & inibidores , RNA Neoplásico/antagonistas & inibidores , RNA Neoplásico/biossíntese , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Telomerase/antagonistas & inibidores , Telomerase/genética , Transcrição Gênica , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/virologia