A genome-wide association study identified LMO1, which encodes an LIM-domain-only transcriptional cofactor, as a neuroblastoma susceptibility gene that functions as an oncogene in high-risk neuroblastoma. Here we show that dβh promoter-mediated expression of LMO1 in zebrafish synergizes with MYCN to increase the proliferation of hyperplastic sympathoadrenal precursor cells, leading to a reduced latency and increased penetrance of neuroblastomagenesis. The transgenic expression of LMO1 also promoted hematogenous dissemination and distant metastasis, which was linked to neuroblastoma cell invasion and migration, and elevated expression levels of genes affecting tumor cell-extracellular matrix interaction, including loxl3, itga2b, itga3, and itga5. Our results provide in vivo validation of LMO1 as an important oncogene that promotes neuroblastoma initiation, progression, and widespread metastatic dissemination.

中文翻译：

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LMO1与MYCN协同促进神经母细胞瘤的启动和转移。

全基因组关联研究确定，仅编码LIM域的转录辅因子的LMO1是神经母细胞瘤易感基因，在高危神经母细胞瘤中起癌基因的作用。在这里，我们显示了斑马鱼中dβh启动子介导的LMO1表达与MYCN协同作用，以增加增生性交感肾上腺前体细胞的增殖，从而导致潜伏期缩短和成神经细胞生成的渗透率增加。LMO1的转基因表达还促进了血源性播散和远处转移，这与神经母细胞瘤细胞的侵袭和迁移有关，并且影响肿瘤细胞与细胞外基质相互作用的基因的表达水平升高，包括loxl3，itga2b，itga3和itga5。