BCAT1-Mediated N-Myc Stabilization Contributes to Tumorigenesis of MYCN-Amplified Neuroblastoma
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ABSTRACT: Neuroblastoma (NB) is a common neuroendocrine tumor in early childhood, and the poor prognosis of high-risk NB is due to its poorly differentiated characteristics and immunosuppressive microenvironment. Around 25% of high-risk NB in children is caused by MYCN gene amplification. In this study, we found that Branched-chain amino acid transaminase 1 (BCAT1) is overexpressed in NB, especially those with MYCN amplification, and is a positively correlated with MYCN expression. Moreover, BCAT1 may be a risk factor for NB, significantly affecting proliferation of NB cells. Besides, we revealed that MYCN directly regulated BCAT1 transcription through binding to BCAT1 promoter, thus enhancing BCAT1-MYCN cooperativity. The highly disordered loop region of the MYCN protein makes it readily degraded under natural conditions, making it difficult to obtain the real structure of MYCN through experiments. We performed GROMACs optimization on the MYCN structure obtained from Alphafold, which increased the reliability of the MYCN structure and met the requirements of subsequent protein docking experiments. In this study, we found that after BCAT1 binds to the disordered regions of MYCN, it can improve the overall stability of MYCN. Therefore, we hypothesized that BCAT1 can enhance the stability of MYCN, suggesting that BCAT1 may be a potential therapeutic target for MYCN-amplified NB. In summary, these findings establish BCAT1 is a critical oncogenic factor in NB and provide a new potential target for treatment of NB with MYCN amplification.
ORGANISM(S): Homo sapiens
PROVIDER: GSE267875 | GEO | 2025/04/01
REPOSITORIES: GEO
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