Reduction of LPAR1 Expression in Neuroblastoma Promotes Tumor Cell Migration.

Reduction of LPAR1 Expression in Neuroblastoma Promotes Tumor Cell Migration.
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DOI:
10.3390/cancers14143346
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发表时间:
2022-07-09
期刊:
影响因子:
5.2
通讯作者:
Gui, Jingang
Gui, Jingang
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Xiangjun;Pei, Mengmiao;Yu, Yongbo;Wang, Xiaolin;Gui, Jingang

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高危神经母细胞瘤患者的骨髓或其他器官转移是一个严重的问题,严重影响患者的生存。神经母细胞瘤治疗的新的和有效的靶点,特别是肿瘤转移,需要探索。利用多个数据库和分析方法,通过我们全面的生物信息学分析筛选出LPAR 1,发现其与神经母细胞瘤患者的生存率呈正相关。与非癌细胞相比,成神经细胞瘤细胞中的LPAR 1被证明是降低的。LPA-LPAR 1轴对神经母细胞瘤细胞具有迁移抑制作用,提示LPAR 1可能是未来神经母细胞瘤治疗的潜在靶点。神经母细胞瘤是儿童最常见的颅外实体瘤。高风险NB患者的肿瘤转移是影响患者生存的重要问题。在这项研究中,我们的目的是使用一个全面的生物信息学分析,以确定NB和对照细胞之间的差异表达基因,并探索新的肿瘤预后标志物或治疗靶点。通过KEGG、GO和PPI网络分析,筛选出FN 1、PIK 3R 5、LPAR 6和LPAR 1,并对LPAR 1的表达和功能进行了实验验证。我们的研究证实LPA可降低NB细胞中LPAR 1的表达,并通过LPAR 1抑制NB细胞的肿瘤迁移。此外,LPAR 1的敲低促进NB细胞的迁移,并取消由LPA-LPAR 1介导的迁移抑制作用。LPA-LPAR 1轴的肿瘤抑制作用表明,LPAR 1可能是未来治疗NB的潜在靶点。
The tumor metastasis in the bone marrow or other organs in high-risk neuroblastoma patients is a serious problem to tackle and strongly impairs the survival of patients. Novel and effective targets for the treatment of neuroblastoma, especially tumor metastasis, need to be explored. Using multiple databases and analysis methods, LPAR1 was screened out through our comprehensive bioinformatics analysis and found to be positively associated with survival of neuroblastoma patients. LPAR1 was proved to be reduced in neuroblastoma cells compared with non-mailgant cells. LPA-LPAR1 axis showed migration-inhibitory effects on neuroblastoma cells, suggesting that LPAR1 may be a potential target for future treatment of neuroblastoma. Neuroblastoma is the most common extracranial solid tumor in children. Tumor metastasis in high-risk NB patients is an essential problem that impairs the survival of patients. In this study, we aimed to use a comprehensive bioinformatics analysis to identify differentially expressed genes between NB and control cells, and to explore novel prognostic markers or treatment targets in tumors. In this way, FN1, PIK3R5, LPAR6 and LPAR1 were screened out via KEGG, GO and PPI network analysis, and we verified the expression and function of LPAR1 experimentally. Our research verified the decreased expression of LPAR1 in NB cells, and the tumor migration inhibitory effects of LPA on NB cells via LPAR1. Moreover, knockdown of LPAR1 promoted NB cell migration and abolished the migration-inhibitory effects mediated by LPA-LPAR1. The tumor-suppressing effects of the LPA-LPAR1 axis suggest that LPAR1 might be a potential target for future treatment of NB.
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