Effects of small nucleolar RNA SNORD44 on the proliferation, apoptosis and invasion of glioma cells

Histochem Cell Biol. 2020 Apr;153(4):257-269. doi: 10.1007/s00418-020-01848-y. Epub 2020 Feb 15.

Abstract

To master the effect of small nucleolar RNA, SNORD44, on the proliferation, apoptosis and invasion of glioma cells and its relevant mechanism. SNORD44 and GAS5 expression in glioma tissues and cells was detected through qRT-PCR. Then, the glioma cell lines (U87 and U251) were divided into different groups with different treatments. Cell proliferation was determined by MTT assay, while the abilities of the cell migration and invasion were measured by wound-healing test and Transwell assay, respectively. Cell apoptosis were detected by flow cytometry and TUNEL assay. The expression of apoptosis proteins was quantified through Western blotting. Finally, the xenograft models were established on nude mice to investigate the effects of SNORD44 on the growth of glioma and the expressions of Ki67, MMP2 and MMP9 in vivo. SNORD44 and GAS5 were down-regulated in glioma tissues and cells in a positive correlation. Either SNORD44 or GAS5 overexpression decreased the proliferation, invasion and migration of U87 and U251 cells with the up-regulation of apoptosis rates, as well as the expressions of cleaved PARP, caspase 3, caspase 8 and caspase 9. Moreover, the in vivo experiment showed that overexpression of SNORD44 blocked the growth of glioma xenograft in nude mice accompanying with the inhibition of Ki67, MMP2 and MMP9 expressions. The combination overexpression of SNORD44 and GAS5 gained better inhibitory effects on glioma cells. Overexpression of SNORD44 and GAS5 activate the caspase-dependent apoptosis pathway to facilitate the apoptosis with the inhibited proliferation, invasion and migration of glioma cells.

Keywords: Apoptosis; GAS5; Glioma; Proliferation; SNORD44; Small nucleolar RNA.

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Line
  • Cell Proliferation
  • Central Nervous System Neoplasms / genetics
  • Central Nervous System Neoplasms / metabolism*
  • Central Nervous System Neoplasms / pathology*
  • Female
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA, Small Nucleolar / genetics
  • RNA, Small Nucleolar / metabolism*

Substances

  • GAS5 long non-coding RNA, human
  • RNA, Long Noncoding
  • RNA, Small Nucleolar