ELK1-induced upregulation of lncRNA TRPM2-AS promotes tumor progression in gastric cancer by regulating miR-195/ HMGA1 axis

J Cell Biochem. 2019 Oct;120(10):16921-16933. doi: 10.1002/jcb.28951. Epub 2019 May 19.


Long noncoding RNAs (lncRNAs) have been confirmed to be aberrantly expressed in various diseases including tumors. Recently, a new tumor-related lncRNA, lncRNA TRPM2 antisense RNA (TRPM2-AS), was shown to be involved in many tumors, such as lung cancer and breast cancer. However, the expression and role of TRPM2-AS in the development of gastric cancer (GC) have not been elucidated. In the current study, we provided evidence that the expression levels of TRPM2-AS were increased in both GC tissues and cell lines. We also showed that overexpression of TRPM2-AS was modulated by ELK1, a transcription factor. The results of clinical assays showed that higher expressions of TRPM2-AS were significantly related with invasion depth, TNM stage, lymphatic metastasis, and shorter overall survival. Further clinical assays using multivariate analysis suggested that TRPM2-AS expression was an independent prognostic factor in patients with GC. Functional experiments illustrated that depression of TRPM2-AS suppressed proliferation, migration, and invasion in GC cells. In terms of mechanism, we found that TRPM2-AS directly inhibited miR-195, which targeted the 3'-untranslated region of high-mobility group AT-hook 1 (HMGA1) messenger RNA. Overall, these findings revealed that ELK1-induced overexpression of TRPM2-AS promoted the development and progression of GC in part through miR-195/HMGA1 signaling axis, and established its candidacy as a new cancer biomarker for GC patients.

Keywords: gastric cancer; high-mobility group AT-hook 1; long noncoding RNA TRPM2-AS; miR-195; prognosis.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • HMGA1a Protein / biosynthesis
  • HMGA1a Protein / genetics*
  • Humans
  • Lymphatic Metastasis / genetics
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • RNA Interference
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics
  • RNA, Small Interfering / genetics
  • Signal Transduction / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • ets-Domain Protein Elk-1 / genetics*


  • ELK1 protein, human
  • HMGA1 protein, human
  • MIRN195 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • ets-Domain Protein Elk-1
  • HMGA1a Protein