circNRIP1 impairs tumorigenesis of colorectal cancer by sponging IGF2BP1 and decreasing NACC1 mRNA stability.

IF 4.2 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology Report Pub Date : 2025-06-20 eCollection Date: 2025-01-01 DOI:10.1093/gastro/goaf041

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

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引用次数: 0

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 in vitro and in vivo. 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 in vitro 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 m⁶A reader activity, and further reduced the stability of NACC1 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.

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circNRIP1通过抑制IGF2BP1和降低NACC1 mRNA的稳定性来损害结直肠癌的肿瘤发生。

背景：结直肠癌（CRC）是世界范围内最致命的恶性肿瘤之一。早期诊断是治疗结直肠癌的关键。需要更方便和准确的早期诊断生物标志物。然而，环状rna （circRNAs）是否参与结直肠肿瘤发生及其在结直肠癌早期诊断中的作用尚不清楚。方法：我们研究了基因表达综合数据库和exoRBase中解除调控的环状rna和crc特异性血外泌体环状rna。在体外和体内进行功能测定，以评估hsa_circ_0004771 （circNRIP1）对增殖和肿瘤发生的影响。通过RNA下拉、蛋白质组学分析和RNA免疫沉淀-聚合酶链反应来探索circNRIP1在结直肠癌发生中的潜在生物学功能。结果：circNRIP1在结直肠癌患者的肿瘤组织中显著下调，在血液外泌体中显著升高。敲低circNRIP1可显著促进体外培养的crc细胞增殖和集落形成能力，提高异种移植小鼠模型的肿瘤形成能力。机制上，circNRIP1与IGF2BP1的K同源y_1/2结构域相互作用，阻断其m6A读取器活性，进一步降低NACC1 mRNA的稳定性，抑制结直肠肿瘤的发生。结论：circNRIP1在结直肠癌肿瘤发生过程中是一个重要的抑癌因子，血外泌体circNRIP1可能是结直肠癌早期诊断的生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gastroenterology Report Medicine-Gastroenterology

CiteScore

4.60

自引率

2.80%

发文量

审稿时长

8 weeks

期刊介绍： Gastroenterology Report is an international fully open access (OA) online only journal, covering all areas related to gastrointestinal sciences, including studies of the alimentary tract, liver, biliary, pancreas, enteral nutrition and related fields. The journal aims to publish high quality research articles on both basic and clinical gastroenterology, authoritative reviews that bring together new advances in the field, as well as commentaries and highlight pieces that provide expert analysis of topical issues.