LncRNA PLAC2 down-regulates RPL36 expression and blocks cell cycle progression in glioma through a mechanism involving STAT1

J Cell Mol Med. 2018 Jan;22(1):497-510. doi: 10.1111/jcmm.13338. Epub 2017 Sep 18.

Abstract

Current glioma therapies allow in situ delivery of cytotoxic drugs to the tumour; however, gliomas show early recurrence due to their highly proliferative character. Long non-coding (lnc)RNAs play critical roles in tumorigenesis by controlling cell proliferation and cycling. However, the mechanism of action of lncRNAs in glioma development remains unclear. Here, we report that the lncRNA PLAC2 induces cell cycle arrest by targeting ribosomal protein (RP)L36 in glioma. RPL36 promoted cell proliferation and G1/S cell cycle progression. Mass spectrometry analysis revealed that signal transducer and activator of transcription (STAT)1 interacted with both lncRNA PLAC2 and the RPL36 promoter. We also found that the nucleus PLAC2 bind with STAT1 and interact with RPL36 promoters but the cytoplasmic lncRNA PLAC2 inhibited STAT1 nuclear transfer, thereby decreasing RP36 expression, inhibiting cell proliferation and inducing cell cycle arrest. These results provide evidence for a novel cell cycle regulatory network in glioma comprising the lncRNA PLAC2 along with STAT1 and RPL36 that can serve as a therapeutic target for glioma treatment.

Keywords: RPL36; STAT1; cell cycle; glioma; lncRNA PLAC2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Cycle / genetics*
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation / genetics*
  • Female
  • G1 Phase / genetics
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics*
  • Glioma / pathology*
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Models, Biological
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Ribosomal Proteins / genetics*
  • Ribosomal Proteins / metabolism
  • S Phase / genetics
  • STAT1 Transcription Factor / metabolism*

Substances

  • RNA, Long Noncoding
  • RPL36A protein, human
  • Ribosomal Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human