Regulation of tumor angiogenesis: Roles of lncRNAs in molecular signaling, microenvironmental remodeling, and anti-angiogenic therapy.

Angiogenesis is a crucial step in the growth and metastasis of invasive tumors. Tumor-induced angiogenesis is not due to a single factor; it involves activation of oncogenic signaling pathways and abnormal expression of angiogenesis-related genes within the complex tumor microenvironment (TME). Traditional research has primarily focused on the regulation of angiogenesis by protein-coding genes. In recent years, growing evidence has shown that long non-coding RNAs (lncRNAs) play important roles in angiogenesis. In this study, we systematically elucidate the molecular mechanisms by which lncRNAs regulate tumor-associated angiogenesis, including epigenetic, transcriptional, and post-transcriptional regulation. Furthermore, lncRNAs indirectly influence angiogenesis by regulating the functions of endothelial cells, cancer-associated fibroblasts, and tumor-associated macrophages within the TME. In addition, lncRNA-targeted therapeutic strategies have been summarized with specific emphasis on their potential integration with anti-angiogenic tumor therapy, including oligonucleotide-based silencing, restoration of tumor-suppressive lncRNAs, anti-vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) combination strategies, and nanomaterial-mediated delivery systems. This review aims to provide a theoretical foundation for innovative research on vascular targeted therapy for tumors.