p53-targeted lncRNA ST7-AS1 acts as a tumour suppressor by interacting with PTBP1 to suppress the Wnt/β-catenin signalling pathway in glioma

Cancer Lett. 2021 Apr 10:503:54-68. doi: 10.1016/j.canlet.2020.12.039. Epub 2021 Jan 19.

Abstract

Glioma is the most prevalent intracranial tumour, with considerable morbidity. Long non-coding RNAs are important in the biological processes of various cancers. However, little is known about ST7 antisense RNA 1 (ST7-AS1) and its role in glioma progression. ST7-AS1 expression was reduced in glioma tissues and cells in comparison to normal brain tissues. p53 transcriptionally targeted the ST7-AS1 promoter in U251 glioma cells. The targeting significantly inhibited cell migration, invasion, and proliferation, and promoted apoptosis. ST7-AS1 directly bound to and downregulated polypyrimidine tract-binding protein 1 (PTBP1) at the post-transcriptional level. ST7-AS1 overexpression inhibited glioma progression by suppressing Wnt/β-catenin signalling by downregulating PTBP1 expression. Additionally, p53 expression negatively correlated with PTBP1 expression. Glioma progression is regulated by a positive feedback loop involving the p53/ST7-AS1/PTBP1 axis, which might be a promising therapeutic target for glioma treatment.

Keywords: Glioma; Long non-coding RNA ST7-AS1; PTBP1; Positive feedback loop; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Feedback, Physiological
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology*
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics*
  • Humans
  • Male
  • Mice
  • Neoplasm Transplantation
  • Polypyrimidine Tract-Binding Protein / genetics*
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics*
  • Tumor Suppressor Protein p53 / metabolism*
  • Wnt Signaling Pathway

Substances

  • Heterogeneous-Nuclear Ribonucleoproteins
  • PTBP1 protein, human
  • RNA, Long Noncoding
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Polypyrimidine Tract-Binding Protein