MicroRNAs in Tumor Endothelial Cells: Regulation, Function and Therapeutic Applications

卷:12

Review

关键词: LONG NONCODING RNA;    EPITHELIAL-MESENCHYMAL TRANSITION;    PROMOTES ANGIOGENESIS;    GROWTH-FACTOR;    TGF-BETA;    HEPATOCELLULAR-CARCINOMA;    NASOPHARYNGEAL CARCINOMA;    CARDIAC-HYPERTROPHY;    CERVICAL-CANCER;    DOWN-REGULATION;   

DOI  :  10.3390/cells12131692

来源: SCIE

【 摘 要 】

Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating evidence has shown that small single-stranded non-coding microRNAs (miRNAs) act as powerful endogenous regulators of TEC function and blood vessel formation. This systematic review provides an up-to-date overview of these endothelial miRNAs. Their expression is mainly regulated by hypoxia, pro-angiogenic factors, gap junctions and extracellular vesicles, as well as long non-coding RNAs and circular RNAs. In preclinical studies, they have been shown to modulate diverse fundamental angiogenesis-related signaling pathways and proteins, including the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway; the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; the phosphoinositide 3-kinase (PI3K)/AKT pathway; and the transforming growth factor (TGF)-& beta;/TGF-& beta; receptor (TGFBR) pathway, as well as kruppel-like factors (KLFs), suppressor of cytokine signaling (SOCS) and metalloproteinases (MMPs). Accordingly, endothelial miRNAs represent promising targets for future anti-angiogenic cancer therapy. To achieve this, it will be necessary to further unravel the regulatory and functional networks of endothelial miRNAs and to develop safe and efficient TEC-specific miRNA delivery technologies.