MiR-508-3p promotes proliferation and inhibits apoptosis of middle ear cholesteatoma cells by targeting PTEN/PI3K/AKT pathway

Int J Med Sci. 2021 Jul 11;18(14):3224-3235. doi: 10.7150/ijms.60907. eCollection 2021.

Abstract

Cholesteatoma of the middle ear is a common disease in otolaryngology, which can lead to serious intracranial and extracranial complications. Recent studies showed that the dysregulation of microRNA may be involved in the formation of middle ear cholesteatoma. This study aimed to explore the regulatory effect of micro ribonucleic acid 508-3p (miR-508-3p) on proliferation and apoptosis of middle ear cholesteatoma cells and excavate its underlying regulatory mechanism. We found miR-508-3p expression was upregulated in tissues and cells of cholesteatoma which was inversely related to the expression of hsa_circ_0000007. Overexpression of miR-508-3p could notably facilitate cholesteatoma cell proliferation. Luciferase reporter assay showed that miR-508-3p bound the 3'-untranslated region of its downstream mRNA PTEN. Gain and loss of functions of miR-508-3p were performed to identify their roles in the biological behaviors of cholesteatoma cells, including proliferation and apoptosis. Rescue assays confirmed that PTEN could reverse the effect of miR-508-3p overexpression on cell proliferation. In a word, this study validated that the development of cholesteatoma may regulated by hsa_circ_0000007/miR-508-3p/ PTEN/ PI3K/Akt axis.

Keywords: PTEN/ PI3K/Akt pathway; cholesteatoma; hsa_circ_0000007; miR-508-3p; proliferation and apoptosis.

Publication types

  • Observational Study

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adolescent
  • Adult
  • Aged
  • Apoptosis / genetics
  • Case-Control Studies
  • Cell Proliferation / genetics
  • Cholesteatoma, Middle Ear / genetics*
  • Cholesteatoma, Middle Ear / pathology
  • Cholesteatoma, Middle Ear / surgery
  • Ear, Middle / pathology
  • Ear, Middle / surgery
  • Female
  • Gene Expression Regulation
  • HaCaT Cells
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Primary Cell Culture
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Circular / metabolism*
  • Signal Transduction / genetics
  • Young Adult

Substances

  • 3' Untranslated Regions
  • MIRN508 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human