The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
J Pediatr Surg. 2021 Apr;56(4):778-787. doi: 10.1016/j.jpedsurg.2020.10.011. Epub 2020 Oct 17.
Neuroblastoma (NB) is the most common solid tumor in children. Studies showed that long-chain noncoding RNA (lncRNA) HCP5 played an important role in tumorigenesis, but its role in NB remained unclear. This study aims to determine the role of HCP5 in NB and its possible molecular mechanism.
We analyzed the expression levels of miRNA-186-5p and HCP5 in neuroblastoma and neuroblastoma cell lines SHSY-5Y, Kelly, NBL-S and SK-N-AS, and explored their roles.
We found that the HCP5 expression was up-regulated in NB tissues and cells. The higher the HCP5 expression in NB cells, the stronger the ability of clone formation. Down regulation of the HCP5 expression inhibited the proliferation of NB cells and the growth of subcutaneous transplanted tumor in nude mice. HCP5 could competitively bind miR-186-5p, while miR-186-5p could target the 3'-UTR of MAP3K2. The expression level of miR-186-5p was down regulated while the expression level of MAP3K2 was up-regulated in NB tissues. The expression level of HCP5 and miR-186-5p, the expression level of miR-186-5p and MAP3K2 were negatively correlated. The decreased proliferation of NB cells induced by down-regulation of HCP5 expression can be counteracted by miR-186-5p inhibitor or MAP3K2, and vice versa.
This study showed that lncRNA HCP5, as ceRNA, regulated MAP3K2 to promote NB progression through competitive binding of miR-186-5p. We revealed a new signaling pathway that mediates NB, which provided a new target for the diagnosis and treatment of NB.
神经母细胞瘤（NB）是儿童中最常见的实体肿瘤。研究表明，长链非编码 RNA（lncRNA）HCP5 在肿瘤发生中发挥重要作用，但它在 NB 中的作用尚不清楚。本研究旨在确定 HCP5 在 NB 中的作用及其可能的分子机制。
我们分析了 miRNA-186-5p 和 HCP5 在神经母细胞瘤和神经母细胞瘤细胞系 SHSY-5Y、Kelly、NBL-S 和 SK-N-AS 中的表达水平，并探讨了它们的作用。
我们发现 HCP5 在 NB 组织和细胞中的表达上调。NB 细胞中 HCP5 表达越高，克隆形成能力越强。下调 HCP5 表达抑制 NB 细胞的增殖和裸鼠皮下移植瘤的生长。HCP5 可以竞争性结合 miR-186-5p，而 miR-186-5p 可以靶向 MAP3K2 的 3'-UTR。NB 组织中 miR-186-5p 的表达下调，MAP3K2 的表达上调。HCP5 和 miR-186-5p 的表达水平、miR-186-5p 和 MAP3K2 的表达水平呈负相关。下调 HCP5 表达诱导的 NB 细胞增殖减少可以被 miR-186-5p 抑制剂或 MAP3K2 逆转，反之亦然。
本研究表明，lncRNA HCP5 作为 ceRNA 通过竞争性结合 miR-186-5p 调节 MAP3K2 促进 NB 进展。我们揭示了一种新的信号通路，该通路通过调节 NB 来介导 NB，为 NB 的诊断和治疗提供了新的靶点。
