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Papel oncogénico de THOR, un ARN largo no codificante de cáncer conservado
Yasuyuki Hosono1, Yashar S Niknafs2, John R Prensner3
1Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Cell
|December 16, 2017
Resumen
Un nuevo ARN no codificante ultraconservado, THOR, se expresa en los testículos y los cánceres. THOR promueve el crecimiento del cáncer y desempeña un papel en la fertilización y el desarrollo del melanoma, lo que sugiere
Área de la Ciencia:
- Biología molecular
- La genómica
- Investigación del cáncer
Sus antecedentes:
- Los ARN largos no codificantes (ARNlnc) son cada vez más reconocidos por sus diversas funciones biológicas.
- Comprender la función y la regulación de los lncRNA específicos es crucial para descifrar los procesos celulares complejos y los mecanismos de la enfermedad.
Objetivo del estudio:
- Para caracterizar funcionalmente un nuevo lncRNA ultraconservado, THOR (ENSG00000226856).
- Investigar el papel del THOR en el cáncer y su interacción con otros componentes celulares.
Principales métodos:
- Caracterización funcional mediante knockdown y sobreexpresión en líneas celulares y modelos animales.
- Investigación de la interacción de THOR con el IGF2BP1.
- Modelos de pez cebra para evaluar el papel de THOR en la fertilización y el desarrollo de melanoma.
Principales resultados:
- THOR exhibe expresión exclusiva en los testículos y varios cánceres humanos.
- THOR knockdown / sobreexpresión impacta el crecimiento celular / tumoral, lo que indica un papel oncogénico.
- THOR interactúa con el IGF2BP1, contribuyendo a la estabilización del ARNm.
- THOR knockout causa defectos de fecundación; la expresión ectópica acelera el inicio del melanoma en el pez cebra.
Conclusiones:
- THOR es un nuevo y funcionalmente importante lncRNA de cáncer/testículo.
- La estructura y la función de THOR han sufrido una selección evolutiva positiva.
- THOR representa un objetivo terapéutico potencial en el cáncer y la medicina reproductiva.
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