Ethoxy-erianin phosphate inhibits angiogenesis in colorectal cancer by regulating the TMPO-AS1/miR-126-3p/PIK3R2 axis and inactivating the PI3k/AKT signaling pathway

Abstract Colorectal cancer (CRC) is the third most common malignancy, with increasing prevalence and mortality. How the ethoxy-erianin phosphate (EBTP) mediates CRC development remains unclear. Therefore, the current study evaluated the effects of EBTP on the proliferation, migration, and angiogenesis of CRC cells using CCK-8, Wound-healing, Transwell, and Tube formation assays. RNA sequencing and molecular docking techniques helped predict that EBTP could inhibit angiogenesis by regulating PIK3R2 expression while clarifying the mechanism behind EBTP-mediated CRC angiogenesis. Subsequently, several in vitro experiments indicated that PIK3R2 overexpression significantly improved the proliferation, migration, and angiogenesis of CRC cells while knocking down PIK3R2 expression inhibited their proliferation, migration, and angiogenesis. Simultaneously, PIK3R2 expression in CRC cells gradually decreased with increased EBTP concentration and action duration. Moreover, PIK3R2 overexpression in CRC cells could reverse the inhibitory EBTP effect in angiogenesis. Mouse experiments also depicted that EBTP inhibited CRC angiogenesis by down-regulating PIK3R2 expression. In addition, EBTP could inhibit PI3K/AKT pathway activity and indirectly control PIK3R2 expression through the lncRNA TMPO-AS1/miR-126-3p axis. Our findings highlighted that EBTP could inhibit CRC angiogenesis using the TMPO-AS1/miR-126-3p/PIK3R2/PI3k/AKT axis, providing a novel strategy for anti-angiogenic therapy in CRC.