Regulatory roles of non-coding and exosomal RNAs in colorectal cancer: spotlight on angiogenesis

Colorectal cancer (CRC) is a primary contributor to cancer-related mortality, largely due to its high metastatic potential. Although traditional treatments like surgery and chemotherapy have advanced, therapeutic resistance and relapse remain major challenges. Recent research has revealed that non-coding RNAs (ncRNAs) play pivotal roles in CRC progression, particularly by driving angiogenesis. Several classes of ncRNAs, including lncRNAs, miRNAs, and circRNAs, are key regulators of angiogenesis in CRC. For example, miRNAs such as miR-148a and miR-181a influence the VEGF and HIF-1α signaling pathways, which are critical for endothelial cell proliferation and migration. Certain lncRNAs, such as HNF1A-AS1 and UCA1, interact with miRNAs to modulate these pathways. CircRNAs (e.g., circ_0001821 and circ-ERBIN) often function as "miRNA sponges," sequestering angiogenesis-inhibiting miRNAs to promote tumor vascularization. Furthermore, exosomes act as intercellular communication vesicles that transport ncRNAs (miRNAs, circRNAs) within the tumor microenvironment (TME). This process enables cancer cells to remodel their environment and facilitate metastatic dissemination. Specifically, exosomal ncRNAs, such as circ_0000467 and circ_0081069, can regulate angiogenesis-related pathways. This review integrates current findings on the complex interactions between miRNAs, lncRNAs, circRNAs, and exosomal ncRNAs in CRC angiogenesis. Understanding these molecular regulators highlights their potential as novel diagnostic biomarkers and therapeutic targets, which may lead to new targeted treatments that improve CRC patient outcomes by controlling angiogenesis and metastatic spread.