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Desestabilización de la transcripción del supresor de la metástasis a través de la unión TARBP2 de las horquillas del

Hani Goodarzi¹, Steven Zhang¹, Colin G Buss¹

¹Laboratory of Systems Cancer Biology, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.

|July 22, 2014

Resumen

Los investigadores descubrieron nuevas estructuras de ARN (sRSEs) que afectan la metástasis del cáncer de mama. La proteína TARBP2 se une a estos elementos, desestabilizando genes clave y promoviendo la propagación del cáncer, revelando nuevos objetivos terapéuticos.

Área de la Ciencia:

Biología Molecular Biología Molecular
Investigación del cáncer Investigación del cáncer.
ARN Biología Biología ARN

Sus antecedentes:

La regulación de la estabilidad del ARN aberrante es crucial en la enfermedad, incluida la progresión del cáncer.
Los microARN dirigidos al ARNm son conocidos como moduladores post-transcripcionales, pero el papel de los elementos estructurales del ARNm en el cáncer no se ha explorado.

Objetivo del estudio:

Identificar nuevos moduladores post-transcripcionales de la estabilidad del ARNm en el cáncer de mama.
Para investigar el papel de los elementos estructurales del ARN en la metástasis del cáncer.

Principales métodos:

Mediciones de estabilidad de transcripción de genoma completo en líneas isogénicas de cáncer de mama humano.
Marco computacional para buscar secuencias de ARN y estructurar el espacio.
Enfoques bioquímicos para identificar los factores trans que se unen a los elementos estructurales del ARN.

Principales resultados:

Descubrimiento de elementos estructurales de estabilidad del ARN ricos en GC (sRSEs) sobrerrepresentados en células metastásicas.
Identificación de TARBP2 como el sRSEs y elementos similares (TBSEs) que se unen al factor trans.
La sobreexpresión de TARBP2 en células metastásicas y tumores desestabiliza los genes supresores de metástasis APP y ZNF395, promoviendo la invasión y la colonización.

Conclusiones:

TARBP2 juega un papel no canónico en la regulación génica mediante la unión de elementos estructurales de ARNm y la promoción de la desestabilización.
La desestabilización regulada del ARN a través de elementos estructurales gobierna la progresión del cáncer.
APP y ZNF395 funcionan como nuevos inhibidores de la metástasis del cáncer de mama.

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