环状核糖核酸NRIP1通过吸附IGF2BP1并降低mRNA稳定性来损害结直肠癌的肿瘤发生。

circNRIP1 impairs tumorigenesis of colorectal cancer by sponging IGF2BP1 and decreasing mRNA stability.

作者信息

Han Kai, Sui Qiaoqi, Xu Yanbo, Duan Jinling, Peng Jianhong, Yu Long, Li Weihao, He Jiahua, Kong Lingheng, Tang Jinghua, Lin Junzhong, Ding Peirong, Xie Dan, Pan Zhizhong

机构信息

Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China.

Department of Pathology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China.

出版信息

Gastroenterol Rep (Oxf). 2025 Jun 20;13:goaf041. doi: 10.1093/gastro/goaf041. eCollection 2025.

DOI:10.1093/gastro/goaf041

PMID:40584151

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12205946/

Abstract

BACKGROUND

Colorectal cancer (CRC) is one of the most lethal malignancies worldwide. Early diagnosis is critical in CRC treatment. More convenient and accurate biomarkers for early diagnosis are needed. However, whether circular RNAs (circRNAs) participate in colorectal tumorigenesis and their role in early diagnosis of CRC remain unknown.

METHODS

We investigated the deregulated circRNAs and CRC-specific blood exosomal circRNAs in the Gene Expression Omnibus database and exoRBase. Functional assays were performed to evaluate the effects of hsa_circ_0004771 (circNRIP1) on proliferation and tumorigenesis both and . RNA pull-down, proteomic analysis, and RNA immunoprecipitation-polymerase chain reaction were performed to explore the underlying biological functions of circNRIP1 in CRC tumorigenesis.

RESULTS

circNRIP1 was significantly downregulated in tumor tissues and increased in the blood exosomes of CRC patients. Knockdown of circNRIP1 significantly promoted CRC-cell proliferation and colony-forming ability and increased the tumor-formation ability in the xenograft mouse model. Mechanistically, circNRIP1 interacted with the K homology_1/2 domain of IGF2BP1 and blocked its mA reader activity, and further reduced the stability of mRNA and inhibited colorectal tumorigenesis.

CONCLUSIONS

circNRIP1 is an important tumor suppressor in CRC tumorigenesis and blood exosomal circNRIP1 could be an early diagnostic biomarker for CRC.

摘要

背景

结直肠癌（CRC）是全球最致命的恶性肿瘤之一。早期诊断在CRC治疗中至关重要。需要更便捷、准确的早期诊断生物标志物。然而，环状RNA（circRNA）是否参与结直肠癌发生及其在CRC早期诊断中的作用仍不清楚。

方法

我们在基因表达综合数据库和外泌体数据库中研究了失调的circRNA和CRC特异性血液外泌体circRNA。进行功能试验以评估hsa_circ_0004771（circNRIP1）在体内和体外对增殖和肿瘤发生的影响。进行RNA下拉、蛋白质组分析和RNA免疫沉淀-聚合酶链反应，以探索circNRIP1在CRC肿瘤发生中的潜在生物学功能。

结果

circNRIP1在肿瘤组织中显著下调，在CRC患者的血液外泌体中增加。敲低circNRIP1显著促进CRC细胞增殖和集落形成能力，并增加异种移植小鼠模型中的肿瘤形成能力。机制上，circNRIP1与IGF2BP1的KH1/2结构域相互作用，阻断其m6A阅读活性，进一步降低c-Myc mRNA的稳定性并抑制结直肠癌发生。