Selective β2 adrenergic agonist increases Cx43 and miR-451 expression via cAMP-Epac.
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.
Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran 1417755469, Iran.
Hossein
H
Mostafavi
Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran 1417755469, Iran.
Mojtaba
M
Khaksarian
Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran 1417755469, Iran.
Mohammad Taghi
MT
Joghataei
Department of Hematology, Tarbiat Modares University, Tehran 1411713116, Iran.
Masoud
M
Soleimani
Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran 1417755469, Iran.
Gholamreza
G
Hassanzadeh
Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran 1417755469, Iran.
Sanaz
S
Eftekhari
Division of Neuroscience, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran 141775553, Iran.
Mansooreh
M
Soleimani
Division of Neuroscience, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran 141775553, Iran.
Kazem
K
Mousavizadeh
Stem Cell Technology Research Center, Molecular Biology and Genetic Engineering Department, Tehran 1585636473, Iran.
Hajar
H
Estiri
Stem Cell Technology Research Center, Molecular Biology and Genetic Engineering Department, Tehran 1585636473, Iran.
Sedighesadat
S
Ahmadi
Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran 1417755469, Iran.
Mahmoud Reza
MR
Hadjighassem
D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018031:Connexin 43 / Q000235:genetics*; D000242:Cyclic AMP / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D058666:Adrenergic beta-2 Receptor Agonists; D018031:Connexin 43; D020662:Guanine Nucleotide Exchange Factors; C531201:MIRN451 microRNA, human; D035683:MicroRNAs; C116122:RAPGEF3 protein, human; C442864:RAPGEF4 protein, human; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP