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LSD1 mediates MYCN control of epithelial-mesenchymal transition through silencing of metastatic suppressor NDRG1 gene

ABSTRACT: Neuroblastoma (NB) with MYCN amplification is a highly metastatic tumor in children, and unraveling the key players involved in MYCN-induced invasion may identify new targets for therapy. Epithelial-mesenchymal transition (EMT) plays a critical role in promoting metastasis and we have recently determined that MYCN interacts with LSD1, a histone de-methylase flavin oxidase, which has been found to promote EMT. We show here that LSD1 affects motility and invasiveness of NB cells through transcription modulation of the metastasis suppressor NDRG1, N-Myc Downstream-Regulated Gene 1. LSD1 co-localizes with MYCN at the promoter region of the NDRG1 gene and it inhibits its expression. LSD1-inhibition relieves NDRG1 repression induced by MYCN with concomitant block of motility and invasiveness of NB cells, and such effects were recapitulated by overexpressing NDRG1. Moreover, we found that low NRDG1 and high LSD1 levels in NB patients were associated with poor survival. These data suggest that LSD1 inhibition may knock down the ability of MYCN-amplified Neuroblastomas to metastasize. Our findings elucidate a mechanism of how MYCN/LSD1 control motility and invasiveness of NB cells through transcription regulation of NDRG1 expression and they suggest that pharmacological targeting of LSD1 could inhibit the NB metastatic process.

ORGANISM(S): Homo sapiens

PROVIDER: GSE80753 | GEO | 2016/12/31

SECONDARY ACCESSION(S): PRJNA319931

REPOSITORIES: GEO

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