Selective β2 adrenergic agonist increases Cx43 and miR-451 expression via cAMP-Epac

Mol Med Rep. 2014 Jun;9(6):2405-10. doi: 10.3892/mmr.2014.2120. Epub 2014 Apr 8.

Abstract

It has been demonstrated that connexin 43 (Cx43) and microRNAs have significant roles in glioma. Cyclic adenosine monophosphate (cAMP) is suggested to be a regulator of connexins and microRNAs. However, it remains elusive whether cAMP and exchange protein directly activated by cAMP (Epac2), have a regulatory effect on Cx43 and microRNA-451 (miR-451) in astrocytoma cells. We treated 1321N1 astrocytoma cells with a selective β2 adrenergic agonist and a selective Epac activator with and without adenyl cyclase and protein kinase A inhibition. Cx43 and miR-451 expression were measured. Next, we evaluated the effect of miR-451 overexpression on Cx43 expression. Cell proliferation was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results demonstrated that cAMP-Epac2 increased Cx43 and miR-451 expression. However, the alteration of miR-451 expression required a higher dose of drugs. Overexpression of miR-451 had no significant effect on Cx43 expression. The MTT assay showed that cAMP-Epac stimulation and miR-451 overexpression had a synergic inhibitory effect on cell proliferation. These findings may expand our understanding of the molecular biology of glioma and provide new potential therapeutic targets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / pharmacology*
  • Astrocytoma / genetics
  • Astrocytoma / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Connexin 43 / genetics*
  • Cyclic AMP / metabolism*
  • Gene Expression
  • Gene Expression Regulation / drug effects*
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • MicroRNAs / genetics*
  • RNA, Messenger / genetics
  • Receptors, Adrenergic, beta-2 / metabolism
  • Signal Transduction / drug effects

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Connexin 43
  • Guanine Nucleotide Exchange Factors
  • MIRN451 microRNA, human
  • MicroRNAs
  • RAPGEF3 protein, human
  • RAPGEF4 protein, human
  • RNA, Messenger
  • Receptors, Adrenergic, beta-2
  • Cyclic AMP