巨噬细胞极化
癌症研究
外体
肿瘤微环境
结直肠癌
肿瘤进展
微泡
刺
大肠癌小鼠模型的建立
下调和上调
生物
医学
癌症
巨噬细胞
体外
内科学
小RNA
基因
肿瘤细胞
生物化学
工程类
航空航天工程
作者
Yuting Zhang,Jiakun Guo,Liyin Zhang,Ying Li,Kangliang Sheng,Yawei Zhang,Liu Liu,Wenbin Gong,Kun Guo
出处
期刊:Inflammatory Bowel Diseases
[Oxford University Press]
日期:2023-08-25
卷期号:29 (12): 1941-1956
被引量:3
摘要
Abstract 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.
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