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

Eur Rev Med Pharmacol Sci. 2020 Dec;24(24):12748-12756. doi: 10.26355/eurrev_202012_24174.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Tripartite Motif Proteins / genetics
  • Tripartite Motif Proteins / metabolism*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • MIRN493 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Tripartite Motif Proteins
  • TRIM2 protein, human
  • Ubiquitin-Protein Ligases