Oncogenic Biogenesis of pri-miR-17â¼92 Reveals Hierarchy and Competition among Polycistronic MicroRNAs.
Mol Cell
; 75(2): 340-356.e10, 2019 07 25.
Article
en En
| MEDLINE
| ID: mdl-31253575
ABSTRACT
The microRNAs encoded by the miR-17â¼92 polycistron are commonly overexpressed in cancer and orchestrate a wide range of oncogenic functions. Here, we identify a mechanism for miR-17â¼92 oncogenic function through the disruption of endogenous microRNA (miRNA) processing. We show that, upon oncogenic overexpression of the miR-17â¼92 primary transcript (pri-miR-17â¼92), the microprocessor complex remains associated with partially processed intermediates that aberrantly accumulate. These intermediates reflect a series of hierarchical and conserved steps in the early processing of the pri-miR-17â¼92 transcript. Encumbrance of the microprocessor by miR-17â¼92 intermediates leads to the broad but selective downregulation of co-expressed polycistronic miRNAs, including miRNAs derived from tumor-suppressive miR-34b/c and from the Dlk1-Dio3 polycistrons. We propose that the identified steps of polycistronic miR-17â¼92 biogenesis contribute to the oncogenic re-wiring of gene regulation networks. Our results reveal previously unappreciated functional paradigms for polycistronic miRNAs in cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Procesamiento Postranscripcional del ARN
/
MicroARNs
/
Carcinogénesis
Límite:
Humans
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2019
Tipo del documento:
Article
País de afiliación:
Canadá