Li Yunsong, Bi Wei, Han Bing, Yuan Tao, Shi Long, Liu Yang, Sun Huanhuan, Li Xueyan, Gao Xiang
Department of Vascular Surgery, Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Department of Vascular Surgery, Third Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Evid Based Complement Alternat Med. 2021 Mar 1;2021:5597567. doi: 10.1155/2021/5597567. eCollection 2021.
Cerebral infarction is one of the leading causes of death worldwide, in which angiogenesis plays a critical role. On the other hand, accumulating evidence has demonstrated that microRNAs (miRNAs) function as key modulators in the formation and progression of cerebral infarction. However, the molecular mechanisms of miRNAs underlying cerebral infarction-associated angiogenesis remain unclear. In the present study, we indicated that the expression of miR-203 was significantly downregulated in serum samples derived from patients with cerebral infarction and in mice brain samples following middle cerebral artery occlusion (MCAO) compared with healthy controls. , the expression of miR-203 was obviously downregulated in hypoxia-induced human umbilical vein vascular endothelial cells (HUVECs). Functionally, ectopic expression of miR-203 drastically suppressed HUVEC proliferation, invasion, and migration. In addition, SLUG, a zinc finger transcriptional repressor, was identified as a direct target of miR-203 and was negatively correlated with miR-203 expression in MCAO mice and in hypoxia-induced HUVECs. Furthermore, overexpression of SLUG reversed the inhibitory effect of miR-203 on proliferation, invasion, and migration abilities of HUVECs. Taken together, our research provides a novel insight of the miR-203-SLUG axis into cerebral infarction-associated endothelial behaviors and may offer a powerful therapeutic target of cerebral ischemia.
脑梗死是全球主要死因之一，血管生成在其中起关键作用。另一方面，越来越多的证据表明，微小RNA（miRNA）在脑梗死的形成和进展中起关键调节作用。然而，miRNA在脑梗死相关血管生成中的分子机制仍不清楚。在本研究中，我们发现与健康对照相比，脑梗死患者血清样本以及大脑中动脉闭塞（MCAO）后小鼠脑样本中miR-203的表达显著下调。此外，在缺氧诱导的人脐静脉血管内皮细胞（HUVEC）中，miR-203的表达也明显下调。在功能上，miR-203的异位表达显著抑制了HUVEC的增殖、侵袭和迁移。此外，锌指转录抑制因子SLUG被确定为miR-203的直接靶点，并且在MCAO小鼠和缺氧诱导的HUVEC中与miR-203表达呈负相关。此外，SLUG的过表达逆转了miR-203对HUVEC增殖、侵袭和迁移能力的抑制作用。综上所述，我们的研究为miR-203-SLUG轴在脑梗死相关内皮细胞行为方面提供了新的见解，并可能为脑缺血提供一个有力的治疗靶点。
