LIN28B alters ribosomal dynamics to promote metastasis in MYCN-driven malignancy.
J Clin Invest
; 131(22)2021 11 15.
Article
de En
| MEDLINE
| ID: mdl-34779407
ABSTRACT
High expression of LIN28B is associated with aggressive malignancy and poor survival. Here, probing MYCN-amplified neuroblastoma as a model system, we showed that LIN28B expression was associated with enhanced cell migration in vitro and invasive and metastatic behavior in murine xenografts. Sequence analysis of the polyribosome fraction of LIN28B-expressing neuroblastoma cells revealed let-7-independent enrichment of transcripts encoding components of the translational and ribosomal apparatus and depletion of transcripts of neuronal developmental programs. We further observed that LIN28B utilizes both its cold shock and zinc finger RNA binding domains to preferentially interact with MYCN-induced transcripts of the ribosomal complex, enhancing their translation. These data demonstrated that LIN28B couples the MYCN-driven transcriptional program to enhanced ribosomal translation, thereby implicating LIN28B as a posttranscriptional driver of the metastatic phenotype.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Ribosomes
/
Protéines de liaison à l'ARN
/
Protéine du proto-oncogène N-Myc
/
Métastase tumorale
/
Neuroblastome
Type d'étude:
Etiology_studies
Limites:
Humans
Langue:
En
Journal:
J Clin Invest
Année:
2021
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique