MiR-16 exacerbates neuronal cell growth and inhibits cell apoptosis by targeting AKT3 in cerebral ischemia injury

Yijun Song,Bo Wang

doi:10.4314/tjpr.v20i10.6

Abstract

Purpose: To evaluate the role of miR-16 in ischemic neuronal injury.Methods: An oxygen-glucose deprivation (OGD) model of ischemic neuronal injury was established in human brain cortical neuron HCN-2 cell line via hypoxic treatment. The mRNA or protein expressions of miR-16, AKT3, Bax and Bcl-2 were assessed by quantitative real time-polymerase chain reaction (qRTPCR) or western blot assay. Targetscan online software was applied to predict potential targets of miR-16. Cell proliferation was measured by CCK-8 assay while the relationship between miR-16 and AKT3 was determined by Luciferase reporter assay.Results: MiR-16 was overexpressed after OGD treatment. MiR-16 overexpression significantly promoted the proliferation of cortical neurons and inhibited their apoptosis, while miR-16 inhibition produced an opposite effect. The expression of AKT3 was increased after miR-16 inhibition, but it was decreased when miR-16 was overexpressed. In addition, luciferase reporter gene results showed that miR-16 targeted AKT3. Functional experiments showed that AKT3 overexpression reversed the effect of miR-16 overexpression on ischemic injury.Conclusion: MiR-16 regulates neuronal cell growth and cell apoptosis through AKT3 expression.These results present new potential therapeutic targets for the treatment of cerebral ischemic stroke.

Highlights

Cerebral ischemia, a common cerebrovascular problem, is a refractory disease that seriously endangers human health, and it is a major cause of permanent disability in adults [1]
It was found that Bax expression was enhanced, while that of Bcl-2 was inhibited after co-transfection with miR-16 mimic and pcDNA3.1-AKT serine/threonine kinase 3 (AKT3) (Figures 5 C and 5 D), indicating that AKT3 overexpression reversed the enhancing effect of miR-16 mimic on cerebral ischemia
These findings indicate that miR-16 regulated cerebral ischemic injury through targeting of AKT3

Summary

Introduction

A common cerebrovascular problem, is a refractory disease that seriously endangers human health, and it is a major cause of permanent disability in adults [1]. It is associated with high morbidity, mortality and recurrence, as well as slow recovery [2]. Neuronal apoptosis is a major cause of cerebral ischemic injury. Inhibition of apoptosis is important in cerebral ischemic injury treatment. MicroRNAs (miRNAs) affect gene expression through inhibition of translation or induction of mRNA degradation by hybridizing with the 3'-UTR of target genes at posttranscriptional level [4]. Studies have indicated that the expressions miRNAs are altered in cerebral ischemia [5]

Results

Discussion

Conclusion