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MISSION LentiPlex Pooled shRNA Library Screening in Mammalian Cells
Published on: December 21, 2011
Las pantallas de RNAi en ratones identifican los reguladores fisiológicos del crecimiento oncogénico
Slobodan Beronja1, Peter Janki, Evan Heller
1Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology & Development, The Rockefeller University, New York, New York 10065, USA.
Nature
|August 16, 2013
Resumen
Este estudio utilizó pantallas de interferencia de ARN de todo el genoma en ratones para identificar reguladores del desarrollo de la piel y el cáncer. Los investigadores descubrieron nuevos genes, incluidos Mllt6 y β-catenina, que controlan el crecimiento de los tejidos y la hiperproliferación.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología del desarrollo Biología del desarrollo.
- Investigación del cáncer Investigación del cáncer.
Sus antecedentes:
- El crecimiento de los tejidos es un proceso complejo que involucra las capacidades celulares y las interacciones ambientales.
- Comprender el crecimiento de los tejidos es crucial para el desarrollo humano y la investigación del cáncer.
- Las investigaciones anteriores carecían de exámenes genómicos completos in vivo para los reguladores del crecimiento tisular.
Objetivo del estudio:
- Para realizar las primeras pantallas mediadas por interferencia de ARN en todo el genoma en ratones.
- Identificar los reguladores del crecimiento epidérmico embrionario y la hiperplasia oncogénica.
- Validar el papel de los reguladores identificados en los cánceres de ratón y humanos.
Principales métodos:
- Se realizaron pantallas de interferencia de ARN en todo el genoma en ratones.
- Centrado en el desarrollo de la piel y la hiperplasia oncogénica inducida por Hras ((G12V).
- Resultados validados en modelos de cáncer en ratones y humanos.
Principales resultados:
- Se han identificado nuevos y conocidos reguladores del crecimiento epidérmico embrionario.
- Mllt6 y la β-catenina fueron los principales éxitos, manteniendo la hiperproliferación dependiente de Hras ((G12V).
- La β-catenina antagoniza el crecimiento epidérmico normal a través de la adhesión independiente de Wnt.
Conclusiones:
- Las investigaciones de todo el genoma de mamíferos in vivo son factibles para diseccionar el desarrollo de tejidos y la tumorigénesis.
- Los reguladores de crecimiento oncogénicos identificados proporcionan objetivos potenciales para las terapias contra el cáncer.
- Este trabajo establece un marco para futuros estudios sobre el crecimiento de los tejidos y el cáncer.
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