Li You-Mei, Liu Xue-Yuan
Department of Neurology, Yangpu Hospital, Tongji University School of Medicine Shanghai 20090, China.
Department of Neurology, Shanghai Tenth People's Hospital of Tongji University Shanghai 200072, China.
Am J Transl Res. 2016 Oct 15;8(10):4242-4249. eCollection 2016.
We and others have reported that the serum procalcitonin (PCT) level has a demonstrative role in predicting the long-term mortality after acute ischemic stroke (AIS) in Chinese population. Nevertheless, the underlying mechanisms remain ill-defined. In the current study, we further detected a close association of stool microRNA-637 (miR-637) levels with the long-term mortality after AIS in Chinese population. Moreover, the serum PCT and stool miR-637 levels appeared to be inversely correlated. AIS patients with lower levels of stool miR-637 appeared to predict more severe mortality in the long-term. Since PCT has been shown to be mainly produced by the neuroendocrine cells in the intestine, we used an intestine neuroendocrine cell line to study the relationship between miR-637 and PCT. Bioinformatics analyses showed that miR-637 targeted the 3'-UTR of PCT mRNA to inhibit its translation, and thus the levels of PCT protein production and secretion, which was proved by luciferase reporter assay. Together, our data reveal that the molecular mechanisms underlying application of serum PCT and stool miR-637 in prognosis of AIS, in which miR-637 in intestine neuroendocrine cells may be reduced during AIS to allow more PCT to be released into serum to be detected.
我们和其他研究人员已经报道，在中国人群中，血清降钙素原（PCT）水平在预测急性缺血性卒中（AIS）后的长期死亡率方面具有指示作用。然而，其潜在机制仍不清楚。在本研究中，我们进一步检测到中国人群中粪便微小RNA-637（miR-637）水平与AIS后的长期死亡率密切相关。此外，血清PCT水平与粪便miR-637水平呈负相关。粪便miR-637水平较低的AIS患者似乎预示着长期死亡率更高。由于已证明PCT主要由肠道神经内分泌细胞产生，我们使用一种肠道神经内分泌细胞系来研究miR-637与PCT之间的关系。生物信息学分析表明，miR-637靶向PCT mRNA的3'-非翻译区以抑制其翻译，从而降低PCT蛋白的产生和分泌水平，荧光素酶报告基因检测证实了这一点。总之，我们的数据揭示了血清PCT和粪便miR-637在AIS预后中应用的分子机制，即AIS期间肠道神经内分泌细胞中的miR-637可能减少，从而使更多的PCT释放到血清中被检测到。
