Computational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer.
Nat Commun
; 8: 14917, 2017 04 11.
Article
en En
| MEDLINE
| ID: mdl-28397780
ABSTRACT
Androgen-ablation therapies, which are the standard treatment for metastatic prostate cancer, invariably lead to acquired resistance. Hence, a systematic identification of additional drivers may provide useful insights into the development of effective therapies. Numerous microRNAs that are critical for metastasis are dysregulated in metastatic prostate cancer, but the underlying molecular mechanism is poorly understood. We perform an integrative analysis of transcription factor (TF) and microRNA expression profiles and computationally identify three master TFs, AR, HOXC6 and NKX2-2, which induce the aberrant metastatic microRNA expression in a mutually exclusive fashion. Experimental validations confirm that the three TFs co-dysregulate a large number of metastasis-associated microRNAs. Moreover, their overexpression substantially enhances cell motility and is consistently associated with a poor clinical outcome. Finally, the mutually exclusive overexpression between AR, HOXC6 and NKX2-2 is preserved across various tissues and cancers, suggesting that mutual exclusivity may represent an intrinsic characteristic of driver TFs during tumorigenesis.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias de la Próstata
/
Regulación Neoplásica de la Expresión Génica
/
Biología Computacional
/
MicroARNs
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
China