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Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

2010, Número 1

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Rev Invest Clin 2010; 62 (1)


RNA de interferencia: biogénesis, mecanismos moleculares y sus aplicaciones en cáncer cervical

Peralta-Zaragoza O, Bermúdez-Morales VH, Madrid-Marina V

Idioma: Español
Referencias bibliográficas: 137
Paginas: 63-80
Archivo PDF: 150.38 Kb.


RESUMEN

El mecanismo de RNA de interferencia (RNAi) es un proceso natural por el cual las células de eucariontes silencian la expresión de genes, a través de la generación de RNA pequeños de interferencia (siRNA) de secuencia complementaria con el RNA mensajero (mRNA). En este proceso, los siRNA de 21-25 nucleótidos de longitud, conocidos como MicroRNA, se asocian con el complejo de silenciamiento inducido por RNAi (RISC), el cual señaliza y degrada los mRNA complementarios por rompimiento endonucleolítico, o bien, reprimen la traducción del transcrito. Adicionalmente, es posible usar secuencias de DNA para transcribir siRNA con características idénticas a los MicroRNA bioactivos, para silenciar la expresión de genes exógenos durante las infecciones virales. La infección persistente por el virus de papiloma humano (HPV) es el principal agente etiológico asociado al desarrollo del cáncer cervical y los oncogenes E6 y E7 de HPV, que están involucrados en la transformación e inmortalización celular, representan blancos estratégicos para silenciar su expresión por siRNA. En varios estudios in vitro e in vivo se ha demostrado que al introducir siRNA dirigidos contra los oncogenes E6 y E7 en células cervicales tumorales humanas transformadas por HPV, se genera el silenciamiento eficiente de los oncogenes E6 y E7, lo cual induce la acumulación de los productos de los genes supresores de tumores p53 y pRb, se activa la muerte celular por apoptosis, y se puede evitar la progresión del proceso tumoral. Por lo tanto, el propósito de la presente revisión es analizar el proceso de biogénesis de los MicroRNA en el mecanismo del silenciamiento de la expresión de genes, y discutir los protocolos con el uso de siRNA como una potencial estrategia de terapia génica para el tratamiento del cáncer cervical.


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