[HTML][HTML] LIN28B alters ribosomal dynamics to promote metastasis in MYCN-driven malignancy

P Missios, EL da Rocha, DS Pearson… - The Journal of …, 2021 - Am Soc Clin Investig
P Missios, EL da Rocha, DS Pearson, J Philipp, MM Aleman, M Pirouz, D Farache…
The Journal of Clinical Investigation, 2021Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation