Long noncoding RNA LINC01410 promotes the tumorigenesis of neuroblastoma cells by sponging microRNA-506-3p and modulating WEE1

Cancer Med. 2020 Nov;9(21):8133-8143. doi: 10.1002/cam4.3398. Epub 2020 Sep 4.

Abstract

Objective: Neuroblastoma (NBL) is an extra-cranial solid tumor in children. This study was attempted to investigate the regulatory mechanism of long noncoding RNA LINC01410 (LINC01410) on NBL.

Methods: The expression of LINC01410, miR-506-3p, and WEE1 in NBL was evaluated by quantitative real time polymerase chain reaction. The proliferation and colony formation ability of NBL cells were analyzed by MTT and colony formation assay. Flow cytometry assay was executed to measure the apoptosis and cell cycle. Dual-luciferase reporter assay was used to detect the targeted relationships among LINC01410, miR-506-3p, and WEE1. Additionally, the role of LINC01410 on NBL in vivo was evaluated according to a tumor xenograft model.

Results: The expression of LINC01410 and WEE1 was enhanced and miR-506-3p was inhibited in NBL. LINC01410 knockdown attenuated the cell proliferation, colony formation ability, and inhibited tumor growth. Moreover, LINC01410 silencing facilitated the apoptosis and arrested the cell cycle. LINC01410 interacted with miR-506-3p to elevate the WEE1 expression in NBL. Additionally, miR-506-3p inhibition or WEE1 overexpression weakened the reduction effects of sh-LINC01410 on cell proliferation, colony formation ability, apoptosis, and cell cycle.

Conclusions: Knockdown of LINC01410 inhibited the development of NBL by miR-506-3p/WEE1 axis in vitro, which could serve as a potential therapeutic target for NBL therapy.

Keywords: WEE1; long noncoding RNA LINC01410; microRNA-506-3p; neuroblastoma; proliferation.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinogenesis / genetics*
  • Cell Cycle Checkpoints / genetics
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression
  • Gene Knockdown Techniques
  • Humans
  • Infant
  • Male
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Transplantation
  • Neuroblastoma / genetics*
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Tumor Burden / genetics
  • Tumor Stem Cell Assay

Substances

  • Cell Cycle Proteins
  • MIRN506 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Protein-Tyrosine Kinases
  • WEE1 protein, human