The Long Non-Coding RNA TP73-AS1 Interacted With miR-142 to Modulate Brain Glioma Growth Through HMGB1/RAGE Pathway

J Cell Biochem. 2018 Apr;119(4):3007-3016. doi: 10.1002/jcb.26021. Epub 2017 Dec 26.

Abstract

P73 antisense RNA 1T (non-protein coding), also known as TP73-AS1 or PDAM, is a long non-coding RNA which may regulate apoptosis via regulation of p53-dependent anti-apoptotic genes. An abnormal change of TP73-AS1 expression was noticed in cancers. The effects of TP73-AS1 in brain glioma growth and the underlying mechanism remain unclear so far. In the present study, TP73-AS1 was specifically upregulated in brain glioma tissues and cell lines, and was associated with poorer prognosis in patients with glioma. TP73-AS1 knocking down suppressed human brain glioma cell proliferation and invasion in vitro, as well as HMGB1 protein. MiR-142 has been reported to play a pivotal role in cancers; here we observed that TP73-AS1 and miR-142 could negatively regulate each other. Results from luciferase assays suggested that TP73-AS1 might compete with HMGB1 for miR-142 binding. Further, HMGB1/RAGE was involved in TP73-AS1/miR-142 regulation of glioma cell proliferation and invasion. In glioma tissues, TP73-AS1 and HMGB1 expression was up-regulated, whereas miR-142 expression was down-regulated. Data from the present study revealed that TP73-AS1 promoted the brain glioma growth and invasion through acting as a competing endogenous RNA (ceRNA) to promote HMGB1 expression by sponging miR-142. In conclusion, we regarded TP73-AS1 as an oncogenic lncRNA promoting brain glioma proliferation and invasion, and a potential target for human brain glioma treatment. J. Cell. Biochem. 119: 3007-3016, 2018. © 2017 Wiley Periodicals, Inc.

Keywords: BRAIN GLIOMA; TP73-AS1; iASPP; lncRNA; miR-142.

MeSH terms

  • Antigens, Neoplasm / genetics
  • Brain Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Glioma / genetics*
  • HMGB1 Protein / genetics
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Mitogen-Activated Protein Kinases / genetics
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Signal Transduction*
  • Survival Analysis
  • Up-Regulation

Substances

  • Antigens, Neoplasm
  • HMGB1 Protein
  • HMGB1 protein, human
  • MIRN142 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA KIAA0495, human
  • MOK protein, human
  • Mitogen-Activated Protein Kinases