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Un circuito de retroalimentación inflamatoria de HNF4α-miRNA regula la oncogénesis hepatocelular

Maria Hatziapostolou¹, Christos Polytarchou, Eleni Aggelidou

¹Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

|December 14, 2011

Resumen

La inhibición transitoria del factor nuclear 4α de los hepatocitos (HNF4α) desencadena el cáncer de hígado a través de un circuito inflamatorio de microARN. La restauración de este circuito con miR-124 previene y trata la carcinogénesis hepatocelular sin efectos secundarios.

Área de la Ciencia:

Hepatología Hepatología.
Biología Molecular Biología Molecular
Investigación del cáncer Investigación del cáncer.

Sus antecedentes:

El factor nuclear hepatocitario 4α (HNF4α) es crucial para el desarrollo y la función del hígado.
La desregulación de HNF4α está implicada en enfermedades del hígado.

Objetivo del estudio:

Para investigar el papel de la inhibición de HNF4α en la transformación hepatocelular.
Para identificar los mecanismos moleculares subyacentes a la carcinogénesis hepática mediada por HNF4α.
Para explorar el potencial terapéutico de dirigirse a un bucle de retroalimentación inflamatoria microRNA específico.

Principales métodos:

Inhibición transitoria de HNF4α en las células hepáticas.
Análisis del microARN y las vías de señalización inflamatoria (miR-124, IL6R, STAT3, miR-24, miR-629).
Estudios in vivo que evalúan la administración sistémica de miR-124 para la prevención y tratamiento del cáncer.

Principales resultados:

La inhibición del HNF4α inicia la transformación hepatocelular a través de un bucle de retroalimentación microARN-inflamatorio.
Este circuito mantiene la supresión de HNF4α y promueve la oncogénesis.
La administración sistémica de miR-124 previene y suprime la carcinogénesis hepatocelular al inducir la apoptosis específica del tumor sin toxicidad.
El circuito HNF4α identificado está alterado en los carcinomas hepatocelulares humanos.

Conclusiones:

Un nuevo bucle de retroalimentación microARN-inflamatorio que involucra a HNF4α, miR-124 y STAT3 impulsa el cáncer de hígado.
La administración sistémica de miR-124 representa una estrategia terapéutica prometedora para el carcinoma hepatocelular.
Dirigirse a este circuito ofrece el potencial para tratar el cáncer de hígado con efectos secundarios mínimos.

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