LncRNA SNHG20 promoted the proliferation of glioma cells via sponging miR-4486 to regulate the MDM2-p53 pathway

Eur Rev Med Pharmacol Sci. 2019 Jun;23(12):5323-5331. doi: 10.26355/eurrev_201906_18199.

Abstract

Objective: Evidence demonstrated the critical role of long noncoding RNAs (lncRNAs) in the initiation and development of human cancers. LncRNA small nucleolar RNA host gene 20 (SNHG20) was recently reported to promote the progression of several cancers; however, the function of SNHG20 in glioma has not been characterized.

Patients and methods: Differential expression of SNHG20 in glioma tissues and cell lines was analyzed by RT-qPCR. Cell Counting Kit-8 (CCK-8) assay was performed to detect the cell viability. The targets prediction was analyzed with the TargetScan database. Western blot was performed to check the protein expression.

Results: SNHG20 was overexpressed in glioma tissues and cell lines. Down-regulation of SNHG20 suppressed the proliferation, migration and induced apoptosis of glioma cells. Molecular studies uncovered that SNHG20 acted as a competing endogenous RNA (ceRNA) to sponge the expression of miR-4486. MiR-4486 was down-regulated in glioma tissues and significantly inversely correlated with the expression of SNHG20. Restoration of miR-4486 remarkably attenuated the promotion effect of SNHG20 on the growth of glioma cells. Further study revealed that miR-4486 targeted the E3 ubiquitin ligase mouse double minute 2 (MDM2) and negatively regulated the expression of MDM2. Down-regulation of MDM2 by miR-4486 increased the abundance of p53 in glioma cells.

Conclusions: We identified the functional mechanism by which SNHG20 modulated the malignancy of glioma cells via targeting the miR-4486/MDM2/p53 pathway. Interrupting the expression of SNHG20 might be a novel strategy to suppress the progression of glioma.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Glioma / genetics*
  • Glioma / pathology
  • Glioma / surgery
  • Humans
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • Signal Transduction / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • MIRN4486 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • long non-coding RNA SNHG20, human
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2