miR-208a-3p suppresses cell apoptosis by targeting PDCD4 in gastric cancer

Oncotarget. 2016 Oct 11;7(41):67321-67332. doi: 10.18632/oncotarget.12006.

Abstract

Programmed cell death 4 (PDCD4) is a novel tumor suppressor gene and a promising target for anticancer therapies. PDCD4 is frequently downregulated in various human cancers; however, the molecular mechanism accounting for the loss expression of PDCD4 in cancers is not fully understood. In this study, we identified specific targeting sites for miR-208a-3p in the 3'-untranslated region (3'-UTR) of the PDCD4 gene which regulated PDCD4 expression. We demonstrated that miR-208a-3p suppressed apoptosis in gastric cancer cells by targeting PDCD4. We also showed that miR-208a-3p promoted the development of tumor growth in xenograft mice by negatively regulating PDCD4. Taken together, this study revealed a critical role for miR-208a-3p as an oncogenic miRNA in gastric carcinogenesis and it may provide a potential novel target for gastric cancer diagnosis and therapy.

Keywords: PDCD4; apoptosis; gastric cancer; miR-208a-3p; microRNA.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins / biosynthesis*
  • Apoptosis Regulatory Proteins / genetics
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / genetics*
  • Heterografts
  • Humans
  • Mice
  • Mice, SCID
  • MicroRNAs / genetics*
  • RNA-Binding Proteins / biosynthesis*
  • RNA-Binding Proteins / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*

Substances

  • Apoptosis Regulatory Proteins
  • MIRN208 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RNA-Binding Proteins