Abstract
BackgroundLong noncoding RNAs (lncRNAs) play essential roles in tumor progression. However, the functions and targets of lncRNAs in neuroblastoma (NB) progression still remain to be determined. In this study, we aimed to investigate the effect of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) on NB and the underlying mechanism involved.MethodsThrough mining of public microarray datasets, we identify aberrantly expressed lncRNAs in NB. The gene expression levels were determined by quantitative real-time PCR, and protein expression levels were determined by western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, wound-healing assay, transwell invasion assays and flow cytometry analysis were utilized to examine cell proliferation, migration, invasion and apoptosis. Luciferase reporter assay was performed to confirm the interaction between DLX6-AS1and its potential targets. Tumor xenograft assay was used to verify the role of DLX6-AS1 in NB in vivo.ResultsWe identified DLX6-AS1 was upregulated in NB by using a public microarray dataset. The expression of DLX6-AS1 was increased in NB tissues and derived cell lines, and high expression of DLX6-AS1 was positively correlated with advanced TNM stage and poor differentiation. Knockdown of DLX6-AS1 induced neuronal differentiation, apoptosis and inhibited the growth, invasion, and metastasis of NB cells in vitro and impaired tumor growth in vivo. MiR-107 was the downstream target of DLX6-AS1. MiR-107 was found to target brain‐derived neurotrophic factor (BDNF) which is an oncogene in NB. Knockdown of miR-107 or overexpression of BDNF reversed the suppression of NB progression caused by DLX6-AS1 silence.ConclusionOverall, our finding supports that DLX6-AS1 promotes NB progression by regulating miR-107/BDNF pathway, acting as a novel therapeutic target for NB.
Highlights
IntroductionLong noncoding RNAs (lncRNAs) play essential roles in tumor progression
Long noncoding RNAs play essential roles in tumor progression
DLX6‐AS1 expression is upregulated in NB Initially, microarray dataset (GSE16476) [12] of 88 NB patients was acquired from Gene Expression Omnibus (GEO)
Summary
Long noncoding RNAs (lncRNAs) play essential roles in tumor progression. The functions and targets of lncRNAs in neuroblastoma (NB) progression still remain to be determined. We aimed to investi‐ gate the effect of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) on NB and the underlying mechanism involved. The biological behavior of NB is extensively heterogeneous, ranging from spontaneous regression to rapid progression [2]. NB patients, many therapeutic modalities fail to improve the clinical outcome [2]. Better elucidating the mechanisms for the aggressive progression of NB is needed for improving the therapeutic efficiencies. Increasing researches have illustrated that lncRNAs are involved in multiple biological processes including cell proliferation, cell cycling, apoptosis, and metastasis.
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