Referencia

Cancer Cell (2010) 18: 303–315

Autores

Melo SA, Moutinho C, Ropero S, Calin GA, Rossi S, Spizzo R, Fernandez AF, Davalos V, Villanueva A, Montoya G, Yamamoto H, Schwartz Jr, Esteller M.

Resumen

El articulo revela que un subgrupo de tumores del colon, estómago y útero secuestran precursores de microRNAs dentro del núcleo no podiendo progredir su biogenesis hasta microRNAs maduros. Los tumores descritos presentan una mutación en una proteína denominada Exportina-5 que en una celula sana actúa como taxista llevando los microRNAs desde el núcleo al citoplasma, pero en estos cánceres es incapaz de conducirlos fuera del núcleo por lo que se pierde su capacidad protectora antitumoral y se observa una disregulacion general de los microRNAs maduros en estas células tumorales.

Descripción

The global impairment of mature microRNAs (miRNAs) is emerging as a common feature of human tumors. One interesting scenario is that defects in the nuclear export of precursormiRNAs (pre-miRNAs) might occur in transformed cells. Exportin 5 (XPO5) mediates pre-miRNA nuclear export and herein we demonstrate the presence of XPO5-inactivating mutations in a subset of human tumors with microsatellite instability. The XPO5 genetic defect traps pre-miRNAs in the nucleus, reduces miRNA processing, and diminishes miRNA-target inhibition. The XPO5 mutant form lacks a C-terminal region that contributes to the formation of the pre-miRNA/XPO5/Ran-GTP ternary complex and pre-miRNAs accumulate in the nucleus. Most importantly, the restoration of XPO5 functions reverses the impaired export of pre-miRNAs and has tumor suppressor features.

Imágen artículo Diciembre

REFERENCIA DEL GRUPO E INVESTIGADOR
Sónia Melo ha realizado la tesis doctoral en el laboratorio de Epigenética del Cáncer dirigido por el Dr. Manel Esteller en el Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona. Su investigación ha estado centrada en las alteraciones genéticas y epigenéticas que afectan la actividad de los microRNAs en cáncer humano.

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