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LINC00839 Promotes Neuroblastoma Progression by Sponging miR-454-3p to Up-Regulate NEUROD1

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Abstract

Neuroblastoma (NB) is the most common extracranial solid malignancy in children. Increasing long non-coding RNAs (lncRNAs) are reported to be associated with NB tumorigenesis and aggressiveness. Here, we attempted to investigate the biological functions of LINC00839 in NB progression as well as its possible pathogenic mechanisms. Public microarray datasets were applied to unearth the abnormally expressed lncRNAs in NB. RT-qPCR analysis was used to measure the expression of LINC00839, miR-454-3p, and neuronal differentiation 1 (NEUROD1) mRNA. The protein level was determined by a western blot assay. CCK-8, plate clone formation, EdU, wound-healing scratch, and transwell assays were employed to evaluate cell proliferation, migration, and invasion. Xenografts were developed in nude mice to determine the effects of LINC00839 on NB tumor growth. Dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments were performed to identify the interaction between miR-454-3p and LINC00839 or NEUROD1. According to GSE datasets (GSE16237 and GSE16476), LINC00839 was found as a potential driver of NB progression. LINC00839 expression was higher in NB tumor tissues and cells. Also, LINC00839 expression was positively correlated with MYCN amplification, advanced INSS stages, and worse prognosis. Silencing of LINC00839 suppressed cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, LINC00839 could act as a sponge of miR-454-3p to facilitate the expression of its target NEUROD1. Moreover, miR-454-3p was demonstrated to exert an anti-cancer activity in NB. More importantly, the tumor-suppressive properties mediated by LINC00839 knockdown were significantly counteracted by the inhibition of miR-454-3p or overexpression of NEUROD1. Our study demonstrates that LINC00839 exerts an oncogenic role in NB through sponging miR-454-3p to up-regulate NEUROD1 expression, deepening our comprehension of lncRNA involved in NB and providing access to the possibility of LINC00839 as a therapeutic target for NB.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Ultrasound, Xi’an Children’s Hospital, No. 69 Xijuyuan Road, Lianhu District, Xi’an, 710003, China

    Qian Zhang, Jingli Wei, Na Li & Bailing Liu

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  1. Qian Zhang
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Correspondence to Bailing Liu.

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Zhang, Q., Wei, J., Li, N. et al. LINC00839 Promotes Neuroblastoma Progression by Sponging miR-454-3p to Up-Regulate NEUROD1. Neurochem Res 47, 2278–2293 (2022). https://doi.org/10.1007/s11064-022-03613-0

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  • DOI: https://doi.org/10.1007/s11064-022-03613-0

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