MiR-210-3p-EphrinA3-PI3K/AKT axis regulates the progression of oral cancer

J Cell Mol Med. 2020 Apr;24(7):4011-4022. doi: 10.1111/jcmm.15036. Epub 2020 Mar 17.

Abstract

This study aimed to explore new therapeutic targets to improve the survival rate of patients with oral squamous cell carcinoma (OSCC).MiR-210-3p, EphrinA3 and EMT related indices were evaluated in OSCC tissues and cell lines. In addition, the relationship between differential EphrinA3 expression and tumour progression was explored through molecular biology techniques, in vitro functional experiments and tumour xenotransplantation models. The expression of EphrinA3 (rs = -0.719, P < .05) and E-cadherin (rs = -0.856, P < .05) was negatively correlated with the pathological grading in OSCC tissues. Protein clustering shows EphrinA3 may be associated with tumour progression. EphrinA3 also can regulate the biological behaviour of oral cancer cells. And it regulates the EMT by the PI3K/AKT signalling pathway. MiR-210-3p targeted the gen EFNA3. Up-regulation of miR-210-3p expression can decrease the expression of EphrinA3 and further to influence the biological behaviour of OSCC. The miR-210-3p-EphrinA3-PI3K/AKT signalling axis plays an important role in the progress of OSCC. EphrinA3 may serve as a novel target for oral cancer treatment.

Keywords: cancer biology; cell signalling; epithelial-mesenchymal interactions; gene expression; gene therapy/therapeutics; oral carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Disease-Free Survival
  • Ephrin-A3 / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Heterografts
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / pathology

Substances

  • Ephrin-A3
  • MIRN210 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-akt