长链非编码 RNA LINC00200 通过与胰岛素样生长因子 2 mRNA 结合蛋白 3（IGF2BP3）结合，增强 Zic 家族成员 2（ZIC2）mRNA 的稳定性，从而促进 MYCN 扩增神经母细胞瘤的恶性进展。

The long noncoding RNA LINC00200 promotes the malignant progression of MYCN-amplified neuroblastoma via binding to insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) to enhance the stability of Zic family member 2 (ZIC2) mRNA.

机构信息

Department of General Surgery, Children's Hospital of Nanjing Medical University, Nanjing 210008, China.

Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing 210008, China.

出版信息

Pathol Res Pract. 2022 Sep;237:154059. doi: 10.1016/j.prp.2022.154059. Epub 2022 Aug 5.

DOI:10.1016/j.prp.2022.154059

PMID:35969939

Abstract

OBJECTIVES

Neuroblastoma (NB) is one of the most common extracranial malignant tumors in children and remarkable heterogeneous tumor of the sympathetic nervous system. Long noncoding RNAs (lncRNAs) have been reported to be vital biological roles in the initiation and malignant progression of tumors. The aim of this study was to explore the biological role and the possible molecular mechanism of LINC00200 in NB.

DESIGN & METHODS: The expression level of LINC00200 in NB tissues and cell lines were detected by real-time quantitative PCR (qRT-PCR). The biological effects of LINC00200 on NB cell proliferation, migration and invasion were examined by EdU and transwell assays. The molecular mechanism of LINC00200 in NB were explored and verified by bioinformatics analysis, RNA binding protein immunoprecipitation (RIP) assay and RNA pull down assay.

RESULTS

The results showed that the expression of LINC00200 was significantly higher in NB tissues than in normal tissues. Besides, the expression of LINC00200 was higher in MYCN Amplified NB tissues than in MYCN non-Amplified NB tissues. Moreover, overexpression of LINC00200 could remarkedly promote proliferation, migration and invasion of NB cell. Mechanistically, LINC00200 might bind to RNA binding protein (RBP) IGF2BP3 and promote the expression of ZIC2.

CONCLUSIONS

Overall, we showed that LINC00200 was upregulated in NB tissues and the LINC00200/IGF2BP3/ZIC2 regulatory axis might be the possible therapeutic target for NB.

摘要

目的

神经母细胞瘤（NB）是儿童最常见的颅外恶性肿瘤之一，也是交感神经系统的显著异质性肿瘤。长链非编码 RNA（lncRNA）已被报道在肿瘤的发生和恶性进展中具有重要的生物学作用。本研究旨在探讨 LINC00200 在 NB 中的生物学作用及其可能的分子机制。

设计与方法

采用实时定量 PCR（qRT-PCR）检测 NB 组织和细胞系中 LINC00200 的表达水平。通过 EdU 和 Transwell 实验检测 LINC00200 对 NB 细胞增殖、迁移和侵袭的生物学影响。通过生物信息学分析、RNA 结合蛋白免疫沉淀（RIP）实验和 RNA 下拉实验探讨和验证 LINC00200 在 NB 中的分子机制。

结果

结果表明，LINC00200 在 NB 组织中的表达明显高于正常组织。此外，在 MYCN 扩增的 NB 组织中，LINC00200 的表达高于 MYCN 非扩增的 NB 组织。此外，过表达 LINC00200 可以显著促进 NB 细胞的增殖、迁移和侵袭。机制上，LINC00200 可能与 RNA 结合蛋白（RBP）IGF2BP3 结合，并促进 ZIC2 的表达。