RNA-binding protein HuR sequesters microRNA-21 to prevent translation repression of proinflammatory tumor suppressor gene programmed cell death 4

Oncogene. 2016 Mar 31;35(13):1703-15. doi: 10.1038/onc.2015.235. Epub 2015 Jul 20.


Translation control of proinflammatory genes has a crucial role in regulating the inflammatory response and preventing chronic inflammation, including a transition to cancer. The proinflammatory tumor suppressor protein programmed cell death 4 (PDCD4) is important for maintaining the balance between inflammation and tumorigenesis. PDCD4 messenger RNA translation is inhibited by the oncogenic microRNA, miR-21. AU-rich element-binding protein HuR was found to interact with the PDCD4 3'-untranslated region (UTR) and prevent miR-21-mediated repression of PDCD4 translation. Cells stably expressing miR-21 showed higher proliferation and reduced apoptosis, which was reversed by HuR expression. Inflammatory stimulus caused nuclear-cytoplasmic relocalization of HuR, reversing the translation repression of PDCD4. Unprecedentedly, HuR was also found to bind to miR-21 directly, preventing its interaction with the PDCD4 3'-UTR, thereby preventing the translation repression of PDCD4. This suggests that HuR might act as a 'miRNA sponge' to regulate miRNA-mediated translation regulation under conditions of stress-induced nuclear-cytoplasmic translocation of HuR, which would allow fine-tuned gene expression in complex regulatory environments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Line, Tumor
  • ELAV-Like Protein 1 / genetics
  • ELAV-Like Protein 1 / metabolism*
  • Genes, Tumor Suppressor
  • HEK293 Cells
  • Humans
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism
  • MCF-7 Cells
  • MicroRNAs / metabolism*
  • Protein Binding
  • Protein Biosynthesis / genetics
  • RNA Interference*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*


  • 3' Untranslated Regions
  • Apoptosis Regulatory Proteins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • Inflammation Mediators
  • MIRN21 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RNA-Binding Proteins