Eur Rev Med Pharmacol Sci 2018; 22 (16): 5270-5277
DOI: 10.26355/eurrev_201808_15726

High expression of GAS5 promotes neuronal death after cerebral infarction by regulating miR-365a-3p

Y.-Z. Liu, Y. Sun

Department of Neurology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China. byqf_2011@163.com


OBJECTIVE: To investigate whether growth arrest specific5 (GAS5) could regulate the expression of DCDC2 through competitive binding to miR-365a-3p, thus leading to increased neuronal death in cerebral cortex.

MATERIALS AND METHODS: The expression levels of GAS5 and DCDC2 in cerebral cortical neurons of mice with mouse middle cerebral artery occlusion (MCAO) cerebral infarction and in control mice were detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Meanwhile, the expression levels of GAS5 and DCDC2 in primary neurons cultured in vitro were also detected by qRT-PCR. The effects of GAS5 and DCDC2 on neuronal death were evaluated by calculating the cerebral infarct area by Tunel assay and TTC staining. Dual luciferase reporter assays were performed to detect the binding of miR-365a-3p to GAS5 and DCDC2. Western blot was applied to detect the protein expression of DCDC2, Bcl-2 and Bax after overexpression and knockdown of GAS5.

RESULTS: The expression of GAS5 and DCDC2 were significantly higher in cerebral cortical neurons and primary cultured neurons in vitro than those in control mice, respectively. Inhibition of GAS5 and DCDC2 in primary neurons decreased the neuronal cells death rate, while overexpression of GAS5 and DCDC2 increased the cell death rate. The dual luciferase reporter gene results showed that GAS5 regulated the expression of DCDC2 through competitive binding of miR-365a-3p thus forming a GAS5/miR-365a-3p/DCDC2 regulatory network. In addition, GAS5 inhibited Bcl-2 while promoting the expression of Bax.

CONCLUSIONS: High expression of GAS5 could promote neuronal death after cerebral infarction in mice, possibly through competitive binding to miR-365a-3p and promoting the expression of DCDC2.

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To cite this article

Y.-Z. Liu, Y. Sun
High expression of GAS5 promotes neuronal death after cerebral infarction by regulating miR-365a-3p

Eur Rev Med Pharmacol Sci
Year: 2018
Vol. 22 - N. 16
Pages: 5270-5277
DOI: 10.26355/eurrev_201808_15726