ZRANB2/SNHG20/FOXK1 Axis regulates Vasculogenic mimicry formation in glioma

J Exp Clin Cancer Res. 2019 Feb 11;38(1):68. doi: 10.1186/s13046-019-1073-7.

Abstract

Background: Glioma is the most common intracranial neoplasm with vasculogenic mimicry formation as one form of blood supply. Many RNA-binding proteins and long non-coding RNAs are involved in tumorigenesis of glioma.

Methods: The expression of ZRANB2, SNHG20 and FOXK1 in glioma were detected by real-time PCR or western blot. The function of ZRANB2/SNHG20/FOXK1 axis in glioma associated with vasculogenic mimicry formation was analyzed.

Results: ZRANB2 is up-regulated in glioma tissues and glioma cells. ZRANB2 knockdown inhibits the proliferation, migration, invasion and vasculogenic mimicry formation of glioma cells. ZRANB2 binds to SNHG20 and increases its stability. Knockdown of SNHG20 reduces the degradation of FOXK1 mRNA by SMD pathway. FOXK1 inhibits transcription by binding to the promoters of MMP1, MMP9 and VE-Cadherin and inhibits vasculogenic mimicry formation of glioma cells.

Conclusions: ZRANB2/SNHG20/FOXK1 axis plays an important role in regulating vasculogenic mimicry formation of glioma, which might provide new targets of glioma therapy.

Keywords: FOXK1; Glioma; SNHG20; Vasculogenic mimicry formation; ZRANB2.

MeSH terms

  • Animals
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Glioma / blood supply
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • HEK293 Cells
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Transfection

Substances

  • FOXK1 protein, human
  • Forkhead Transcription Factors
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • ZRANB2 protein, human
  • long non-coding RNA SNHG20, human