Growing evidence indicates that a small number of cancer cells express stem cell markers and possess stem cell-like properties that promote malignant progression. Sex-determining region Y-box2 (SOX2) is a stem cell transcription factor essential for maintaining the properties of cancer stem cell (CSC). As CSC properties have been associated with angiogenesis and vasculogenic mimicry (VM), we aimed to comprehensively investigate whether SOX2 regulates CSC properties, angiogenesis, and VM in colorectal carcinoma (CRC) and its potential mechanism in this study. For this study, sphere formation assay, flow cytometry, cell survival analysis, tube formation, 3D culture, immunoblot, mouse model, and luciferase reporter assay were performed in vivo and in vitro. Expressions of SOX2 and miR-450a-5p in CRC tissue samples were examined through immunohistochemistry. First, the expression of SOX2 was not only associated with poor differentiation and prognosis but also promoted angiogenesis and VM. Knockdown of SOX2 ceased stemness properties, angiogenesis, and VM, along with decreased expression of CD133, CD31, and VE-cadherin as observed in functional experiments. Downregulation of SOX2 was found to inhibit tumorigenesis in vivo. Second, miR-450a-5p suppressed the expression of SOX2 by targeting its 3'UTR region directly and hence restrained SOX2-induced CSC properties, angiogenesis, and VM. Moreover, SOX2 overexpression preserved the miR-450a-5p-induced inhibition of CRC properties, angiogenesis, and VM. Finally, clinical samples exhibited a negative correlation between miR-450a-5p and SOX2. Patients with higher SOX2 and lower miR-450a-5p expressions had a poorer prognosis than patients with inverse expressions. Conclusively, we elucidated a unique mechanism of miR-450a-5p-SOX2 axis in the regulation of stemness, angiogenesis, and VM, which may act as a potential therapeutic practice in CRC.

中文翻译：

---

miR-450a-5p / SOX2轴在结直肠癌中对癌症干细胞特性，血管生成和血管生成模拟的调节。

越来越多的证据表明，少数癌细胞表达干细胞标志物，并具有促进恶性进展的类干细胞特性。性别决定区域Y-box2（SOX2）是维持癌症干细胞（CSC）特性必不可少的干细胞转录因子。由于CSC属性已与血管生成和血管生成模拟物（VM）相关联，因此我们旨在全面研究SOX2是否在结直肠癌（CRC）中调节CSC属性，血管生成和VM及其潜在机制。对于这项研究，在体内和体外进行了球体形成测定，流式细胞术，细胞存活分析，管形成，3D培养，免疫印迹，小鼠模型和荧光素酶报告基因测定。通过免疫组织化学检查CRC组织样品中SOX2和miR-450a-5p的表达。首先，SOX2的表达不仅与不良的分化和预后有关，而且还促进血管生成和VM。如功能实验中所观察到的，击倒SOX2会停止干性，血管生成和VM，以及CD133，CD31和VE-钙黏着蛋白的表达下降。发现SOX2的下调在体内抑制肿瘤发生。其次，miR-450a-5p通过直接靶向3'UTR区域来抑制SOX2的表达，因此抑制了SOX2诱导的CSC特性，血管生成和VM。而且，SOX2过表达保留了miR-450a-5p诱导的CRC特性，血管生成和VM抑制作用。最后，临床样品在miR-450a-5p和SOX2之间显示出负相关。具有较高SOX2和较低miR-450a-5p表达的患者的预后要比具有反向表达的患者差。最后，我们阐明了miR-450a-5p-SOX2轴在干性，血管生成和VM调控中的独特机制，这可能是CRC中潜在的治疗方法。