Enhanced expression of lncRNA TP73-AS1 predicts unfavorable prognosis for gastric cancer and promotes cell migration and invasion by induction of EMT

Gene. 2018 Dec 15:678:377-383. doi: 10.1016/j.gene.2018.08.055. Epub 2018 Aug 16.

Abstract

Gastric cancer (GC) is a deadly disease with high incidence worldwide in recent years. Long noncoding RNAs (lncRNAs) were found to play imperative roles in many biological processes, such as cancer development and progression. Specifically, TP73-AS1, a novel cancer-related lncRNA, was documented to be up-regulated in several malignancies, but the clinical significance and functional role of TP73-AS1 in GC is still unknown. RT-qPCR was performed to evaluate TP73-AS1 transcription in GC tissue specimens and cell lines. In addition, the correlation between TP73-AS1 transcription and clinicopathologic features was further evaluated. Moreover, the effects of TP73-AS1 on GC cell were measured in vitro and in vivo. The data documented that TP73-AS1 was enhanced in GC tissues and cells, and TP73-AS1 transcription level was tightly associated with tumor size, TNM stage, and overall survival in 76 GC patients. What's more, decreased TP73-AS1 could restrain cell growth and colony-forming capacity and promoted apoptosis partly by regulating Bcl-2/caspase-3 pathway. Importantly, TP73-AS1 could promote xenograft growth in vivo. Silencing of TP73-AS1 inhibited GC cell migratory and invasive properties partly by reversing snail-mediated epithelial-to-mesenchymal transition (EMT). Collectively, this study may help to develop the treatment strategy for GC.

Keywords: EMT; Gastric cancer; Long non-coding RNA; TP73-AS1.

MeSH terms

  • Animals
  • Caspase 3 / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Long Noncoding / genetics*
  • Signal Transduction*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • Survival Analysis
  • Tumor Burden
  • Up-Regulation*

Substances

  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Long Noncoding
  • long non-coding RNA KIAA0495, human
  • CASP3 protein, human
  • Caspase 3