The Long Noncoding RNA TP73-AS1 Interacted with miR-124 to Modulate Glioma Growth by Targeting Inhibitor of Apoptosis-Stimulating Protein of p53

DNA Cell Biol. 2018 Feb;37(2):117-125. doi: 10.1089/dna.2017.3941.

Abstract

P73 antisense RNA 1T (non-protein coding), known as TP73-AS1 or PDAM, is a long noncoding RNA (lncRNA), which may regulate apoptosis by regulation of p53-dependent antiapoptotic 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 this study, the effect of TP73-AS1 in human brain glioma cell lines and clinical tumor samples was detected so as to reveal its role and function. In this study, TP73-AS1 was specifically upregulated in brain glioma cell lines and promoted glioma cell growth through targeting miR-124. TP73-AS1 knocking down suppressed human brain glioma cell proliferation, invasion, and metastasis in vitro. The inhibitory effect of TP73-AS1 knocking down on glioma cell proliferation and invasion could partly be restored by miR-124 inhibition. In addition, miR-124-dependent inhibitor of apoptosis-stimulating protein of p53 (iASPP) regulation was required in TP73-AS1-induced brain glioma cell growth. Data from this study revealed that TP73-AS1 inhibited the brain glioma growth and metastasis as a competing endogenous RNA (ceRNA) through miR-124-dependent iASPP regulation. In conclusion, we regarded TP73-AS1 as an oncogenic lncRNA promoting brain glioma proliferation and metastasis and a potential target for human brain glioma treatment.

Keywords: TP73-AS1; glioma; inhibitor of apoptosis-stimulating protein of p53 (iASPP); lncRNA; miR-124.

MeSH terms

  • Base Sequence
  • Binding Sites
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • MIRN124 microRNA, human
  • MicroRNAs
  • PPP1R13L protein, human
  • RNA, Long Noncoding
  • Repressor Proteins
  • long non-coding RNA KIAA0495, human