UNR/CSDE1 Drives a Post-transcriptional Program to Promote Melanoma Invasion and Metastasis
Abstract:
RNA binding proteins (RBPs) modulate cancer progression through poorly understood mechanisms. Here we show that the RBP UNR/CSDE1 is overexpressed in melanoma tumors and promotes invasion and metastasis. iCLIP sequencing, RNA sequencing, and ribosome profiling combined with in silico studies unveiled sets of pro-metastatic factors coordinately regulated by UNR as part of RNA regulons. In addition to RNA steady-state levels, UNR was found to control many of its targets at the level of translation elongation/termination. Key pro-oncogenic targets of UNR included VIM and RAC1, as validated by loss- and gain-of-function studies. Our results identify UNR as an oncogenic modulator of melanoma progression, unravel the underlying molecular mechanisms, and identify potential targets for this therapeutically challenging malignancy.
Año de publicación:
2016
Keywords:
- CSDE1
- UNR
- ribosome profiling
- translation elongation
- Vimentin
- Metástasis
- iCLIP
- RAC1
- melanoma
Fuente:


Tipo de documento:
Article
Estado:
Acceso abierto
Áreas de conocimiento:
- Expresión génica
- Cáncer
Áreas temáticas:
- Fisiología humana
- Enfermedades