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

选择性 β2 肾上腺素能激动剂通过 cAMP-Epac 增加 Cx43 和 miR-451 表达

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作者:Hossein Mostafavi, Mojtaba Khaksarian, Mohammad Taghi Joghataei, Masoud Soleimani, Gholamreza Hassanzadeh, Sanaz Eftekhari, Mansooreh Soleimani, Kazem Mousavizadeh, Hajar Estiri, Sedighesadat Ahmadi, Mahmoud Reza Hadjighassem

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.

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