SMARCE1 promotes neuroblastoma tumorigenesis through assisting MYCN-mediated transcriptional activation

SMARCE1 gene, encoding a core subunit of SWI/SNF chromatin remodeling complex, is situated on chromosome 17q21-ter region that is frequently gained in neuroblastoma. However, its role in the tumorigenesis remains unknown. Here, we showed that high expression of SMARCE1 was associated with poor prognosis of patients with neuroblastoma, especially those with MYCN amplification. Knockdown of SMARCE1 reduced proliferation, colony formation, and tumorigenicity of neuroblastoma cells. Mechanistically, SMARCE1 directly interacted with MYCN, which was necessary for MYCN-mediated transcriptional activation of downstream target genes including PLK1, ODC1, and E2F2. Overexpression of PLK1, ODC1 or E2F2 significantly reversed the inhibiting effect of SMARCE1 knockdown on the proliferation, colony formation, and tumorigenicity of MYCN-amplified neuroblastoma cells. Moreover, we revealed that MYCN directly regulated SMARCE1 transcription through binding to a non-canonical E-box of SMARCE1 promoter, thus enhancing SMARCE1-MYCN cooperativity. These findings establish SMARCE1 is a critical oncogenic factor in neuroblastoma and provide a new potential target for treatment of neuroblastoma with 17q21-ter gain and MYCN amplification.