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. 2016 Dec;44(6):1331-1338.
doi: 10.1177/0300060516665707. Epub 2016 Nov 18.

Decreased plasma miR-335 expression in patients with acute ischemic stroke and its association with calmodulin expression

Bin Zhao  1 , Zilong Zhu  2 , Junwei Hao  1 , Zongming Wan  3 , Xiaoqin Guo  4
Affiliations

Decreased plasma miR-335 expression in patients with acute ischemic stroke and its association with calmodulin expression

Bin Zhao et al. J Int Med Res. 2016 Dec.

Abstract

Objective To determine the expression and clinical significance of plasma miR-335 in patients with acute ischemic stroke (AIS) and investigate its association with calmodulin (CaM) expression. Methods Plasma miR-335 and CaM expression levels in patients with AIS and healthy controls were examined. Correlations between miR-335, CaM, and National Institutes of Health Stroke Scale scores were also analysed. Furthermore, the potential regulatory function of miR-335 on CaM expression was investigated. Results Plasma miR-335 levels were significantly lower in AIS and negatively correlated with NIHSS scores. The converse was observed for plasma CaM levels. Plasma miR-335 and CaM levels were negatively correlated. Plasma miR-335 was confirmed as a novel biomarker for AIS diagnosis and an independent predictor of AIS. Up-regulation of miR-335 suppressed CaM protein expression, and CaM was confirmed as a direct target of miR-335. Conclusions Plasma miR-335 was down-regulated in AIS patients and represents a potential noninvasive circulating biomarker.

Keywords: MicroRNA-335; acute ischemic stroke; calmodulin; diagnosis.

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Figures

Figure 1.
Figure 1.
Plasma miR-335 and Calmodulin (CaM) levels in acute ischemic stroke (AIS) patients and healthy controls. (a) Plasma miR-335 levels in AIS patients were significantly lower than in healthy controls. (b) Plasma miR-335 levels were negatively correlated with NIHSS scores in AIS patients. (c) Plasma CaM levels in AIS patients were significantly higher than in healthy controls. (d). Plasma CaM levels were positively correlated with NIHSS scores in AIS patients. (e) Plasma miR-335 and CaM levels were negatively correlated.
Figure 2.
Figure 2.
Receiver operating characteristics (ROC) curve of plasma miR-335 for the diagnosis of acute ischemic stroke.
Figure 3.
Figure 3.
CaM is a direct target of miR-335. (a) Predicted miR-335 target sequence in the 3′UTR of CaM. (b) Analysis of relative luciferase activities of CaM-WT and CaM-mut (**P > 0.01 versus control [one-way analysis of variance]). (c) miR-335 upregulation in HUVECs was associated with decreased CaM protein levels.
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