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

Sep 21, 2026

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Colorectal cancer (CRC) is the third most common malignancy, with increasing prevalence and mortality. The ethoxy-erianin phosphate (EBTP) mechanism in CRC development remains unclear. This study assessed EBTP effects on CRC cell proliferation, migration, and angiogenesis using CCK-8, wound healing, Transwell, and tube formation assays. RNA sequencing and molecular docking suggested EBTP inhibits angiogenesis by regulating PIK3R2 expression and clarifying CRC angiogenesis mechanisms. Experiments showed PIK3R2 overexpression enhanced, while PIK3R2 knockdown suppressed, proliferation, migration, and angiogenesis; EBTP reduced PIK3R2 with dose and time.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages16

Reading Time40 min

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Abstract

Study rationale and outcomes

EBTP effects on CRC cell behavior

TMPO-AS1/miR-126-3p/PIK3R2 axis and PI3K/AKT inhibition

Liu et al. BMC Cancer (2024) 24:1275 [https://doi.org/10.1186/s12885-024-12893-4](https://doi.org/10.1186/s12885-024-12893-4) BMC Cancer RESEARCH Open Access 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 Liu1,2†, Fei Teng1,2†, Yuxin Lu3†, Yanqing Zhu3, Xin Liang3, Fanhong Wu5,6, Jianwen Liu3,6, Wenming Zhou4*, Chang Su1,2* andYiou Cao1,2* 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, Woundhealing, 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 EBTPmediated 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. Keywords EBTP, Colorectal cancer, Angiogenesis, PIK3R2, TMPO-AS1 †Shaoqun Liu, Fei Teng and Yuxin Lu are co-first authors. *Correspondence: Wenming Zhou [23099145@qq.com](23099145@qq.com)[ ](23099145@qq.com)Chang Su [suchang_jx@126.com](suchang_jx@126.com)[ ](suchang_jx@126.com)Yiou Cao [yioucao_doctor@126.com](yioucao_doctor@126.com) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.org/licenses/by-nc-nd/4.0/.) Liu et al. BMC Cancer (2024) 24:1275 Introduction Colorectal cancer (CRC) is the third most common malignancy worldwide because of risk factors like lack of exercise, low-fiber diet, smoking, and obesity, with its mortality rate ranking second [1, 2]. Current advancesin chemotherapy, targeted therapy, immunotherapy, and other treatments have improved the overall survival of CRC patients. However, the mortality rate of these patients

FAQs

What does ethoxy-erianin phosphate (EBTP) do in colorectal cancer cells?

EBTP inhibits CRC angiogenesis and affects CRC cell proliferation and migration. It reduces PIK3R2 expression in a dose- and time-dependent manner.

How was EBTP’s impact on angiogenesis evaluated?

CRC cells were tested using CCK-8, wound healing, Transwell, and tube formation assays. RNA sequencing and molecular docking were used to predict pathway-related mechanisms.

What molecular axis is implicated in EBTP-mediated angiogenesis inhibition?

EBTP is linked to the TMPO-AS1/miR-126-3p/PIK3R2 axis and inactivates the PI3K/AKT signaling pathway. The study also indicates PIK3R2 overexpression can reverse EBTP’s inhibitory effects.

Sep 21, 2026

Uploaded by Rowan