Aberrant DNA methylation of synaptophysin is involved in adrenal cortisol-producing adenoma

Aging (Albany NY). 2019 Jul 28;11(14):5232-5245. doi: 10.18632/aging.102119.

Abstract

Cortisol-producing adenoma (CPA) is the main cause of Adrenal Cushing syndrome. However, its molecular mechanism is not fully understood. Previous study revealed Synaptophysin (SYP) is ubiquitously expressed in adrenocortical tumors, but its function in CPA still need to be discovered. In the present study we determine the molecular mechanism involved in SYP dysregulation in CPA and how SYP affects the secretion of cortisol in CPA. Our results showed that aberrant DNA methylation of SYP is involved in CPA progress. Using a miRNA microarray and qRT-PCR, we found decreased expression of miR-27a-5p in CPA compared with normal adrenal tissue. Moreover, the expression of TET3, the target gene of miR-27a-5p, increased in CPA compared with normal adrenal tissue. Knock-down of TET3 resulted in hypermethylation of SYP which reducing the expression level of SYP in H295R cells. The miR-27a-5p-TET3-SYP signalling pathway may regulate proliferation and cortisol secretion in H295R cells and, thus, play a key role in CPA development.

Keywords: DNA methylation; adrenal cortisol-producing adenoma; microRNA; synaptophysin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Neoplasms / genetics*
  • Adrenal Cortex Neoplasms / metabolism*
  • Adrenocortical Adenoma / genetics*
  • Adrenocortical Adenoma / metabolism*
  • Adult
  • Cell Line, Tumor
  • DNA Methylation*
  • Dioxygenases / genetics
  • Female
  • Gene Knockdown Techniques
  • Gene Targeting
  • Humans
  • Hydrocortisone / metabolism*
  • Male
  • MicroRNAs / genetics
  • Middle Aged
  • Signal Transduction
  • Synaptophysin / genetics*
  • Up-Regulation

Substances

  • MIRN27 microRNA, human
  • MicroRNAs
  • SYP protein, human
  • Synaptophysin
  • TET3 protein, human
  • Dioxygenases
  • Hydrocortisone