MiR-340 suppresses the metastasis by targeting EphA3 in cervical cancer

Cell Biol Int. 2018 Sep;42(9):1115-1123. doi: 10.1002/cbin.10974. Epub 2018 Jul 11.

Abstract

MicroRNAs (miRNAs) play key roles in cervical cancer metastasis progression. Accumulated evidences have revealed that miRNAs are related to the pathophysiological process. However, the role of miR-340 in cervical cancer and how it works is still not fully interpreted. Using qRT-PCR to examine the expression of miR-340 in cervical cancer tissues. Transwell migration and invasion experiments were used to detect the role of miR-340 in migration and invasion. Luciferase reporter assay, qRT-PCR, and Western blot were used to detect the relationship between miR-340 and EphA3. Using Transwell migration and invasion experiments to investigate the role of EphA3 on migration and invasion. Restoration expriments were also performed. Western blot was used to assay the influence of miR-340 and EphA3 on EMT. We found that miR-340 was downregulated in cervical cancer tissues compared with the normal tissues. Transwell migration and invasion experiments indicated that overexpression of miR-340 frequently inhibited the migration and invasion of cervical cancer cells. EphA3 is a target of miR-340, and ectopic expression of EphA3 can promote the migration and invasion of cervical cancer cells, whereas restoration of EphA3 in miR-340-overexpressing cervical cancer cells reversed the suppressive effects of miR-340. What's more, the process of migration and invasion which regulated by miR-340/EphA3 was depended on adjusting the EMT way. These findings indicate that miR-340 may act as an anti-tumor factor during the process of tumor metastasis through targeting EphA3, suggesting that miR-340 might be a potential new diagnostic and therapeutic molecule for the treatment of cervical cancer.

Keywords: EMT; EphA3; cervical cancer; miR-340; migration and invasion.

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Epithelial-Mesenchymal Transition
  • Female
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, EphA3
  • Transcriptome
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • MIRN340 microRNA, human
  • MicroRNAs
  • EPHA3 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, EphA3