STAT5A induced LINC01198 promotes proliferation of glioma cells through stabilizing DGCR8

Aging (Albany NY). 2020 Apr 4;12(7):5675-5692. doi: 10.18632/aging.102938. Epub 2020 Apr 4.

Abstract

Background: LINC01198 has been suggested to be able to predict overall prognosis for glioma; however, it has been little described in glioma.

Results: It was shown that LINC01198 was markedly enriched in neoplasmic tissues relative to normal controls; and that elevated LINC01198 significantly correlated with unfavorable overall prognosis. Moreover, activation of STAT5A, identified as transcription factor (TF), can induce the expression of LINC01198. DGCR8, a kind of RNA-binding proteins (RBPs), was identified to be able to bind with LINC01198 that can stabilize the DGCR8. Five differential miRNAs with most significant difference, including miR-21-5p, miR-34-5p, miR-1246, miR-4488 and miR-494, were obtainable after silencing of DGCR8.

Conclusions: Together, the data we presented here suggested that STAT5 induced LINC01198 promotes proliferation and motility of glioma cells through stabilizing DGCR8 in glioma cells.

Methods: Expression of LINC01198 was appraised by quantitative PCR (qPCR) and in situ hybridization (ISH) in glioma clinical specimens, totaling 100 cases. Post hoc statistical analysis was conducted. In vitro, LINC01198 was stably silenced or re-expressed by transfection with lentiviral-based vectors. Chromatin-immunoprecipitation (CHIP) was applied to identify the relevant TFs that can bind with LINC01198, which was corroborated with electrophoretic mobility shift (EMSA) assay. RNA-immunoprecipitation (RIP) was used to identify the RNA-binding protein that can bind with LINC01198. Moreover, miRNA microarray was used to screen out differential miRNAs after silencing of DGCR8.

Keywords: DGCR8; LINC001198; STAT5A; glioma; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / physiology*
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • Mice
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • DGCR8 protein, human
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • STAT5 Transcription Factor