Long noncoding RNAs, emerging and versatile regulators of tumor-induced angiogenesis

Angiogenesis is an essential step in maintaining tumor growth and facilitating metastasis. The regulatory mechanisms of tumor-induced angiogenesis are extremely complicated, and include sophisticated crosstalk between tumors and surrounding microenvironment cells, oncogenic signaling pathway activation and aberrant expression of angiogenesis-related genes. Recently, emerging evidence demonstrated that long noncoding RNAs (lncRNAs) play crucial roles in angiogenesis. However, there are lack of reports to review the progression in this scientific field. Here, we focus on and summarize the latest findings of lncRNA in angiogenesis in various cancers. Firstly, we introduced how lncRNAs in tumor cells to modulate the cellular signaling axis, interact with proteins and serve as competitive endogenous RNAs (ceRNAs) to alter target gene expression, by which induce endothelial cell to form capillaries. Then, we recapitulated the essential functions of lncRNA in endothelial cells, and how lncRNAs in tumor-associated macrophages to mediate angiogenesis. Next, the angiogenesis mechanism of tumor-derived lncRNAs via exosomes were collectively described. At last, the effects of lncRNAs on vasculogenic mimicry were summarized, which showed that malignant tumor cells acquire dedifferentiated and endothelial properties to form vessel-like structures by themselves. This review provides new insights into the complexity of angiogenesis, and suggests that lncRNAs may become promising biomarkers and targets for enhancing the efficacy of anti-angiogenesis therapy in cancer.