J Mol Neurosci.2019 May;68(1):144-152.doi: 10.1007/s12031-019-01293-0.Epub 2019 Mar 20.

Neuroprotective Influence of miR-301a Inhibition in Experimental Cerebral Ischemia/Reperfusion Rat Models Through Targeting NDRG2

Tao Feng  1 Bang-Hua Han  1 Gong-Li Yang  1 Chao-Jie Shi  1 Zhen-Wen Gao  1 Ming-Zhi Cao  1 Xiao-Lei Zhu  2 Affiliations

Abstract

The objective of this study is to find out the potential influence of miR-301a in an experimental cerebral ischemia-reperfusion (I/R) rat model through targeting NDRG2. Rats with cerebral I/R injury were constructed and classified into model, miR-301a inhibitor, miR-301a mimic, NC (negative control), siNDRG2, NDRG2, and miR-301a inhibitor + si-NDRG2 groups, as well as another sham group. Cerebral infarct volume and cell apoptosis were observed by TTC staining and TUNEL staining. The targeting relationship between miR-301a and NDRG2 was verified by luciferase assay. ELISA, qRT-PCR, and Western blot were used to detect the expressions of related molecules. Compared with sham group, rats in the model group had elevated neurological function score and infarct volume; meanwhile, the cell apoptosis rate and inflammatory response were also increased with enhanced expression of miR-301a and NDRG2 (all P < 0.05). These changes were worsened in the miR-301a mimic and si-NDRG2 groups. Conversely, those rats in the miR-301a inhibitor and NDRG2 groups presented increased NDRG2, and at the same time, other above concerning factors also exhibited opposite tendencies (all P < 0.05). Dual-luciferase reporter gene assay confirmed that NDRG2 was a target gene of miR-301a, and si-NDRG2 could reverse the neuroprotective effect of miR-301a inhibitor in rats with cerebral I/R injury. Inhibiting miR-301a has a neuroprotective effect on rats with cerebral I/R injury to ameliorate cell apoptosis and inflammatory response through possibly targeting NDRG2.

Keywords: Apoptosis; Cerebral ischemia-reperfusion injury; NDRG2; miR-301a.

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