OIP5-AS1 specifies p53-driven POX transcription regulated by TRPC6 in glioma

J Mol Cell Biol. 2021 Sep 11;13(6):409-421. doi: 10.1093/jmcb/mjab001.

Abstract

Transcription factors (TFs) control an array of expressed genes. However, the specifics of how a gene is expressed in time and space as controlled by a TF remain largely unknown. Here, in TRPC6-regulated proline oxidase 1 (POX) transcription in human glioma, we report that OIP5-AS1, a long noncoding RNA, determines the specificity of p53-driven POX expression. The OIP5-AS1/p53 complex via its 24 nucleotides binds to the POX promoter and is necessary for POX expression but not for p21 transcription. An O-site in the POX promoter to which OIP5-AS1 binds was identified that is required for OIP5-AS1/p53 binding and POX transcription. Blocking OIP5-AS1 binding to the O-site inhibits POX transcription and promotes glioma development. Thus, the OIP5-AS1/O-site module decides p53-controlled POX expression as regulated by TRPC6 and affects glioma development.

Keywords: DNA‒RNA hybrid; glioma; lncRNA; p53; transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Glioma / genetics*
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Proline Oxidase / genetics*
  • RNA, Long Noncoding / genetics*
  • Signal Transduction / genetics
  • TRPC6 Cation Channel / genetics*
  • Transcription, Genetic / genetics*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • RNA, Long Noncoding
  • TP53 protein, human
  • TRPC6 Cation Channel
  • TRPC6 protein, human
  • Tumor Suppressor Protein p53
  • long noncoding RNA OIP5, human
  • Proline Oxidase