SMAD9-MYCN positive feedback loop represents a unique dependency for MYCN-amplified neuroblastoma.

ABSTRACT:

Background

Neuroblastoma (NB) is the most common extracranial solid tumor occurring during childhood and high-risk NB patients have a poor prognosis. The amplified MYCN gene serves as an important determinant of a high risk of NB.

Methods

We performed an integrative screen using public NB tissue and cell line data, and identified that SMAD9 played an important role in high-risk NB. An investigation of the super-enhancers database (SEdb) and chromatin immunoprecipitation sequencing (ChIP-seq) dataset along with biological experiments of incorporating gene knockdown and CRISPR interference (CRISPRi) were performed to identify upstream regulatory mechanism of SMAD9. Gene knockdown and rescue, quantitative real-time PCR (Q-RT-PCR), cell titer Glo assays, colony formation assays,

SUBMITTER: Tan K 

PROVIDER: S-EPMC9764568 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature