Silencing of long non-coding RNA DLX6-AS1 weakens neuroblastoma progression by the miR-513c-5p/PLK4 axis

IUBMB Life. 2020 Dec;72(12):2627-2636. doi: 10.1002/iub.2392. Epub 2020 Oct 8.

Abstract

Emerging evidence has demonstrated the crucial roles of long noncoding RNAs in human cancers, including neuroblastoma (NB). DLX6 antisense RNA 1 (DLX6-AS1) has been identified as an oncogenic driver in NB. However, the mechanisms of DLX6-AS1 in NB progression are not fully understood. Our data showed that DLX6-AS1 was significantly overexpressed in NB tissues and cells. Moreover, DLX6-AS1 silencing repressed NB cell viability, colony formation, migration, and invasion, and promoted cell cycle arrest and apoptosis in vitro, as well as decreased tumor growth in vivo. Mechanistically, DLX6-AS1 operated as a miR-513c-5p sponge. MiR-513c-5p mediated the regulation of DLX6-AS1 on NB cell malignant progression in vitro. PLK4 was a target of miR-513c-5p- and DLX6-AS1-controlled PLK4 expression via sponging miR-513c-5p. Furthermore, the suppressive effect of miR-513c-5p overexpression on NB cell malignant progression in vitro was reversed by PLK4 upregulation. Our findings identified a novel regulatory mechanism, the DLX6-AS1/miR-513c-5p/PLK4 axis, in NB progression, highlighting a strong rationale for developing DLX6-AS1 as a new target for NB management.

Keywords: DLX6-AS1; NB; PLK4; miR-513c-5p; progression.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology*
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA, Antisense / genetics*
  • RNA, Long Noncoding / genetics*
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • DLX6 protein, human
  • Homeodomain Proteins
  • MIRN513A1 microRNA, human
  • MicroRNAs
  • RNA, Antisense
  • RNA, Long Noncoding
  • PLK4 protein, human
  • Protein Serine-Threonine Kinases