miR-302b inhibits cancer-related inflammation by targeting ERBB4, IRF2 and CXCR4 in esophageal cancer

Oncotarget. 2017 Jul 25;8(30):49053-49063. doi: 10.18632/oncotarget.17041.

Abstract

Cancer related inflammation (CRI) plays an important role in the development of esophageal cancer (EC), and the target gene analysis shows that miR-302b potential target genes closely correlated to CRI important signaling pathways. The present study was to evaluate the inhibition of miR-302b on CRI in EC and its mechanism. We found that the expression levels of miR-302b in EC cells were lower than that in Het-1A cells, while TE11 with the lowest expression and OE33 with the highest. Inflammatory stimuli at 48 h significantly reduced expression of miR-302b in EC cells, but had no effect in Het-1A. After up-regulation of miR-302b in TE11 and down-regulation of miR-302b in OE33, it was found that miR-302b reduced CRI key transcription factors and representative cytokines. Then, over-expressed of miR-302b significantly altered potential target genes protein expressions and there was a negative correlation between miR-302b and potential target genes protein expressions (ERBB4, IRF2 and CXCR4) in EC tissues. Then reporter gene analysis revealed that miR-302b post-transcriptionally regulated expression of target genes by specific area of 3'-UTR. Transfected by target genes shRNA plasmids together could get the same effects of miR-302b on protein expression of CRI key transcription factors. Furthermore, miR-302b was able to repress tumor growth and transcription factors protein expression in vivo. These finding suggests that miR-302b inhibits key transcription factors and cytokines by targeting ERBB4, IRF2 and CXCR4, implicating its role in the inhibition of CRI in EC.

Keywords: cancer related inflammation; esophageal cancer; miR-302b.

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Computational Biology / methods
  • Esophageal Neoplasms / complications*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inflammation / complications*
  • Inflammation / genetics*
  • Inflammation / pathology
  • Interferon Regulatory Factor-2 / genetics*
  • MicroRNAs / genetics*
  • RNA Interference
  • Receptor, ErbB-4 / genetics*
  • Receptors, CXCR4 / genetics*

Substances

  • 3' Untranslated Regions
  • Interferon Regulatory Factor-2
  • MIRN302A microRNA, human
  • MicroRNAs
  • Receptors, CXCR4
  • Receptor, ErbB-4