Long non-coding RNA NR2F1-AS1 promoted neuroblastoma progression through miR-493-5p/TRIM2 axis

L. Liu, H. Zhao, H.-H. He, J. Huang, Y.-Y. Xu, X.-L. Li, Y. Wu, J. Wang, Y.-B. Zhu

Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, Jiangsu, China. jianwang@chosu.cn

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• Oncology

OBJECTIVE: Long noncoding RNA (lncRNA) plays a vital role in the progression of various cancers. However, the potential mechanisms of NR2F1-AS1 in the tumorigenesis of neuroblastoma (NB) have not been determined.

PATIENTS AND METHODS: The expression levels of NR2F1-AS1, miR-493 and TRIM2 were detected by RT-qPCR. The downstream target genes of NR2F1-AS1 or miR-493 were predicted by bioinformatics analysis (http://starbase.sysu.edu.cn/), which was further indicated by Luciferase reporter and RNA immunoprecipitation (RIP) assays. CCK-8, transwell, and TUNEL assays were performed to determine the viability, migration, invasion and apoptosis of NB cells.

RESULTS: NR2F1-AS1 was highly expressed and miR-493 was lowly expressed in NB tissues and cell lines. The high expression of NR2F1-AS1 was associated with poor prognosis in NB. NR2F1-AS1 knockdown inhibited proliferation, migration, and invasion, and accelerated apoptosis of NB cells. MiR-493 was a downstream target of NR2F1-AS1, and the silencing of miR-493 reversed NR2F1-AS1 knockdown-attenuated progression of NB. Moreover, TRIM2 was demonstrated to be directly targeted by miR-493, and the upregulation of TRIM2 could abolish the inhibitory effect of miR-493 overexpression on the progression of NB. Finally, it was found that NR2F1-AS1 regulated TRIM2 expression by sponging miR-493.

CONCLUSIONS: The present study demonstrated that NR2F1-AS1 promoted the progression of NB through the miR-493/TRIM2 axis. This finding may provide new insight into the treatment of NB.

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