MAP3K11 is a tumor suppressor targeted by the oncomiR miR-125b in early B cells.
Cell Death Differ
; 23(2): 242-52, 2016 Feb.
Article
de En
| MEDLINE
| ID: mdl-26138442
ABSTRACT
MicroRNAs (miRNAs) are a class of small, non-coding RNAs that posttranscriptionally regulate gene expression and thereby control most, if not all, biological processes. Aberrant miRNA expression has been linked to a variety of human diseases including cancer, but the underlying molecular mechanism often remains unclear. Here we have screened a miRNA expression library in a growth factor-dependent mouse pre-B-cell system to identify miRNAs with oncogenic activity. We show that miR-125b is sufficient to render pre-B cells growth factor independent and demonstrate that continuous expression of miR-125b is necessary to keep these cells in a transformed state. Mechanistically, we find that the expression of miR-125b protects against apoptosis induced by growth factor withdrawal, and that it blocks the differentiation of pre-B to immature B cells. In consequence, miR-125b-transformed cells maintain expression of their pre-B-cell receptor that provides signals for continuous proliferation and survival even in the absence of growth factor. Employing microarray analysis, we identified numerous targets of miR-125b, but only reconstitution of MAP3K11, a critical regulator of mitogen- and stress-activated kinase signaling, interferes with the cellular fitness of the transformed cells. Together, this indicates that MAP3K11 might function as an important tumor suppressor neutralized by oncomiR-125b in B-cell leukemia.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
MAP Kinase Kinase Kinases
/
MicroARN
/
Précurseurs lymphoïdes B
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Female
/
Humans
Langue:
En
Journal:
Cell Death Differ
Année:
2016
Type de document:
Article
Pays d'affiliation:
Allemagne