Long Noncoding RNA pancEts-1 Promotes Neuroblastoma Progression through hnRNPK-Mediated β-Catenin Stabilization
Long Noncoding RNA pancEts-1 Promotes Neuroblastoma Progression through hnRNPK-Mediated β-Catenin Stabilization
复制标题
长非编码 RNA pancEts-1 通过 hnRNPK 介导的 β-Catenin 稳定促进神经母细胞瘤进展
DOI：
10.1158/0008-5472.can-17-2295
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发表时间：
2018-03-01
期刊：
影响因子：
11.2
通讯作者：
Tong, Qiangsong
中科院分区：
文献类型：
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作者：
Li, Dan;Wang, Xiaojing;Tong, Qiangsong
长非编码 RNA (lncRNA) 在肿瘤进展中发挥重要作用。然而，lncRNA 在神经母细胞瘤的肿瘤发生和侵袭性中的功能仍有待确定。在这里，我们通过使用公共微阵列数据集报告了 lncRNA pancEts-1 作为神经母细胞瘤进展的新驱动因素的鉴定。 LncRNA pancEts-1在体外和体内促进神经母细胞瘤细胞的生长、侵袭和转移。从机制上讲，pancEts-1 与 hnRNPK 结合，促进其与 β-连环蛋白的物理相互作用，而 hnRNPK 通过抑制蛋白酶体介导的降解来稳定 β-连环蛋白，导致与神经母细胞瘤进展相关的靶基因的转录改变。 pancEts-1和hnRNPK在临床神经母细胞瘤组织中均上调，并且与患者的不良预后相关。总体而言，我们的结果通过 hnRNPK 介导的 β-catenin 稳定作用定义了 pancEts-1 在神经母细胞瘤进展中的致癌作用，对神经母细胞瘤的临床治疗具有潜在影响。意义：这些发现揭示了长非编码 RNA 在神经母细胞瘤进展中的致癌功能，为临床治疗提供了潜在靶点。 (C) 2018 年 AACR。
Long noncoding RNAs (lncRNA) play essential roles in tumor progression. However, the functions of lncRNAs in the tumorigenesis and aggressiveness of neuroblastoma still remain to be determined. Here, we report the identification of lncRNA pancEts-1 as a novel driver of neuroblastoma progression by using a public microarray dataset. LncRNA pancEts-1 promoted the growth, invasion, and metastasis of neuroblastoma cells in vitro and in vivo. Mechanistically, pancEts-1 bound to hnRNPK to facilitate its physical interaction with beta-catenin, whereas hnRNPK stabilized the beta-catenin by inhibiting proteasome-mediated degradation, resulting in transcriptional alteration of target genes associated with neuroblastoma progression. Both pancEts-1 and hnRNPK were upregulated in clinical neuroblastoma tissues, and were associated with unfavorable outcome of patients. Overall, our results define an oncogenic role of pancEts-1 in neuroblastoma progression through hnRNPK-mediated beta-catenin stabilization, with potential implications for the clinical therapeutics of neuroblastoma.Significance: These findings reveal the oncogenic functions of a long noncoding RNA in neuroblastoma progression, offering a potential target for clinical therapeutics. (C) 2018 AACR.