Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P.R. China.
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P.R. China.
Cancer Res. 2018 Mar 1;78(5):1169-1183. doi: 10.1158/0008-5472.CAN-17-2295. Epub 2018 Jan 8.
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 as a novel driver of neuroblastoma progression by using a public microarray dataset. LncRNA promoted the growth, invasion, and metastasis of neuroblastoma cells and Mechanistically, bound to hnRNPK to facilitate its physical interaction with β-catenin, whereas hnRNPK stabilized the β-catenin by inhibiting proteasome-mediated degradation, resulting in transcriptional alteration of target genes associated with neuroblastoma progression. Both and were upregulated in clinical neuroblastoma tissues, and were associated with unfavorable outcome of patients. Overall, our results define an oncogenic role of in neuroblastoma progression through hnRNPK-mediated β-catenin stabilization, with potential implications for the clinical therapeutics of neuroblastoma. These findings reveal the oncogenic functions of a long noncoding RNA in neuroblastoma progression, offering a potential target for clinical therapeutics. .
长链非编码 RNA（lncRNA）在肿瘤进展中发挥着重要作用。然而，lncRNA 在神经母细胞瘤发生和侵袭性中的作用仍有待确定。在这里，我们通过使用公共微阵列数据集报告了鉴定 lncRNA 作为神经母细胞瘤进展的新型驱动因子。lncRNA 促进神经母细胞瘤细胞的生长、侵袭和转移，并且机制上，与 hnRNPK 结合，促进其与 β-catenin 的物理相互作用，而 hnRNPK 通过抑制蛋白酶体介导的降解稳定 β-catenin，导致与神经母细胞瘤进展相关的靶基因的转录改变。lncRNA 和 hnRNPK 在临床神经母细胞瘤组织中均上调，并与患者的不良预后相关。总之，我们的研究结果通过 hnRNPK 介导的 β-catenin 稳定定义了 lncRNA 在神经母细胞瘤进展中的致癌作用，这对神经母细胞瘤的临床治疗具有潜在意义。这些发现揭示了长链非编码 RNA 在神经母细胞瘤进展中的致癌功能，为临床治疗提供了一个潜在的靶点。
