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
Shaoqun Liu,
Fei Teng,
Yuxin Lu,
Yanqing Zhu,
Xin Liang,
Fanhong Wu,
Jianwen Liu,
Wenming Zhou,
Chang Su,
Yiou Cao
Affiliations
Shaoqun Liu
Department of Gastrointestinal Surgery, Minhang Hospital, Fudan University
Fei Teng
Department of Gastrointestinal Surgery, Minhang Hospital, Fudan University
Yuxin Lu
Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology
Yanqing Zhu
Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology
Xin Liang
Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology
Fanhong Wu
School of Chemical and Environmental Engineering, Shanghai Institute of Technology
Jianwen Liu
Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology
Wenming Zhou
Department of Endoscope Center, Minhang Hospital, Fudan University
Chang Su
Department of Gastrointestinal Surgery, Minhang Hospital, Fudan University
Yiou Cao
Department of Gastrointestinal Surgery, Minhang Hospital, Fudan University
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.
