Network-based, cross-cohort discovery of transcriptional mechanisms presiding over maintenance of high-risk neuroblastoma subtype state

ABSTRACT: Network-based analysis of neuroblastoma samples from two large cohorts identified master regulator proteins controlling the transcriptional state of three high-risk molecular subtypes. In particular, a TEAD4-MYCN positive feedback loop emerged as the core regulatory motif of a small protein module presiding over implementation and stability of the subtype associated with MYCN amplification. Specifically, MYCN transcriptionally activates TEAD4, which in turn activates MYCN both transcriptionally and post-translationally. The resulting MYCN-TEAD4 positive feedback loop plays a critical role in maintaining aberrant activity of a 10-protein regulatory module that causally regulates the transcriptional state of this subtype. Consistently, loss of TEAD4 activity induces core module activity coll

ORGANISM(S): Homo sapiens

SUBMITTER: Gonzalo Lopez 

PROVIDER: E-GEOD-84389 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress