CHD5 抑制神经母细胞瘤的转移。
CHD5 inhibits metastasis of neuroblastoma.
机构信息
Section Experimental Pediatric Oncology, Dept. of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
Institute of Medical Systems Biology, Ulm University, Ulm, Germany.
出版信息
Oncogene. 2022 Jan;41(5):622-633. doi: 10.1038/s41388-021-02081-0. Epub 2021 Nov 17.
CHD5, a tumor suppressor at 1p36, is frequently lost or silenced in poor prognosis neuroblastoma (NB) and many adult cancers. The role of CHD5 in metastasis is unknown. We confirm that low expression of CHD5 is associated with stage 4 NB. Forced expression of CHD5 in NB cell lines with 1p loss inhibited key aspects of the metastatic cascade in vitro: anchorage-independent growth, migration, and invasion. In vivo, formation of bone marrow and liver metastases developing from intravenously injected NB cells was delayed and decreased by forced CHD5 expression. Genome-wide mRNA sequencing revealed reduction of genes and gene sets associated with metastasis when CHD5 was overexpressed. Known metastasis-suppressing genes preferentially upregulated in CHD5-overexpressing NB cells included PLCL1. In patient NB, low expression of PLCL1was associated with metastatic disease and poor survival. Knockdown of PLCL1 and of p53 in IMR5 NB cells overexpressing CHD5 reversed CHD5-induced inhibition of invasion and migration in vitro. In summary, CHD5 is a metastasis suppressor in NB.
CHD5 是 1p36 上的一种肿瘤抑制因子,在预后不良的神经母细胞瘤(NB)和许多成人癌症中经常丢失或沉默。CHD5 在转移中的作用尚不清楚。我们证实 CHD5 的低表达与 4 期 NB 有关。在具有 1p 缺失的 NB 细胞系中强制表达 CHD5,抑制了体外转移级联反应的关键方面:无锚定生长、迁移和侵袭。在体内,从静脉注射的 NB 细胞中形成的骨髓和肝转移的形成被延迟并通过强制表达 CHD5 减少。全基因组 mRNA 测序显示,当 CHD5 过表达时,与转移相关的基因和基因集减少。在 CHD5 过表达的 NB 细胞中优先上调的已知转移抑制基因包括 PLCL1。在患者 NB 中,PLCL1 的低表达与转移性疾病和不良预后相关。在过表达 CHD5 的 IMR5 NB 细胞中敲低 PLCL1 和 p53,逆转了 CHD5 诱导的体外侵袭和迁移抑制。综上所述,CHD5 是 NB 中的一种转移抑制因子。