前人研究指出，体内肿瘤微环境 (TME) 内的通讯介质被认为是外泌体，通过在 TME 内部的癌细胞与其他与癌症有关的细胞之间传递货物来调节癌症进程。环状 RNA (circRNA) 在结直肠癌 (CRC) 进展中被发现是调节因子，但其中大部分尚未在 CRC 中讨论过。本研究旨在调查 circRNA 天冬氨酸β-羟化酶 (circASPH) 在 CRC 进展中的作用以及其与外泌体介导的 TME 的相关性。首先，我们确定了 CRC 样本和细胞系中 circASPH 的上调。功能上，circASPH 缺乏抑制了 CRC 细胞的恶性进程，并通过增强抗肿瘤免疫力抑制了体内肿瘤的生长。在机械上，circASPH 通过上调表达外泌体中的干扰素基因刺激器 (STING) 来促进巨噬细胞 M2 极化。circASPH 与胰岛素样生长因子 2 mRNA 结合蛋白 2 (IGF2BP2) 互作，稳定 IGF2BP2 蛋白，从而增强了 m6A 修饰的 STING mRNA 的稳定性。反过来，STING 过表达的巨噬细胞的共培养恢复了沉默 circASPH 对 CRC 细胞的恶性抑制，无论是在体内还是体外。我们的研究证明 circASPH 增强外泌体 STING 促进 M2 巨噬细胞极化，进一步加速了 CRC 的进展。该发现支持 circASPH 作为 CRC 治疗的有希望的治疗靶点。© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. 若需要权限，请发送电子邮件至: journals.permissions@oup.com。

Exosomes are considered a mediator of communication within the tumor microenvironment (TME), which modulates cancer progression through transmitting cargos between cancer cells and other cancer-related cells in TME. Circular RNAs (circRNAs) have emerged to be regulators in colorectal cancer (CRC) progression, but most of them have not been discussed in CRC. This study aims to investigate the role of circRNA aspartate beta-hydroxylase (circASPH) in CRC progression and its correlation with exosome-mediated TME. At first, we determined that circASPH was upregulated in CRC samples and cell lines. Functionally, the circASPH deficiency suppressed the malignant processes of CRC cells and also inhibited in vivo tumor growth via enhancing antitumor immunity. Mechanically, circASPH facilitated macrophage M2 polarization by upregulating exosomal stimulator of interferon genes (STING). CircASPH interacted with insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) to stabilize IGF2BP2 protein, therefore enhancing the stability of m6A-modified STING mRNA. In turn, coculture of STING-overexpressed macrophages recovered the suppression of silenced circASPH on the malignancy of CRC cells both in vitro and in vivo. Our study demonstrated that circASPH enhances exosomal STING to facilitate M2 macrophage polarization, which further accelerates CRC progression. The findings support circASPH as a promising therapeutic target for CRC treatment.© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.