Stat-3 signaling promotes cell proliferation and metastasis of gastric cancer through PDCD4 downregulation

Kaohsiung J Med Sci. 2020 Apr;36(4):244-249. doi: 10.1002/kjm2.12159. Epub 2019 Dec 20.

Abstract

The present study explored a new downstream regulator of Stat-3 signaling, miR-499-5p and its target gene programmed cell death 4 (PDCD4) in cell survival and metastasis of gastric cancer. Our results showed that miR-499-5p is significantly upregulated in human gastric cancer cell line SGC-7901. We further demonstrated that miR-499-5p promotes gastric cancer cell proliferation and invasion in vitro. Mechanistically, we demonstrated that upregulation of miR-499-5p expression associated with inhibition of PDCD4; STAT3 transcriptional activation by IL-6 is crucial for the upregulation of miR-499-5p expression. These results indicate that the STAT3-miR-499-5p-PDCD4 signaling axis plays an important role in gastric cancer progression and a potentially therapeutic target for gastric cancer treatment.

Keywords: PDCD4; Stat-3; gastric cancer; miR-499-5p.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • Promoter Regions, Genetic / genetics
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*

Substances

  • 3' Untranslated Regions
  • Apoptosis Regulatory Proteins
  • MIRN499 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RNA-Binding Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human