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Hsa_circ_0000467通过吸附miR-520g激活TCF4/Wnt/β-连环蛋白信号通路,从而促进结直肠癌的增殖及干细胞特性。

Hsa_circ_0000467 promotes colorectal cancer proliferation and stem cell characteristics by activating the TCF4/Wnt/β-catenin pathway via sponging miR-520g.

作者信息

Xu Fanggen, Wang Yujing, Liang Rongzhou, Jiang Sicong

机构信息

Gaoxin Branch of The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330038, China.

Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang, Urumqi, Jiangxi 330038, China.

出版信息

APL Bioeng. 2025 Apr 25;9(2):026111. doi: 10.1063/5.0252083. eCollection 2025 Jun.

Abstract

This study explores the role of circ_0000467 in colorectal cancer (CRC) progression and its potential as a therapeutic target. Circ_0000467 expression was analyzed using public datasets and clinical samples from 103 CRC patients. Functional assays evaluated its influence on CRC cell proliferation, migration, and stem-like properties. Molecular interactions with miR-520g and TCF4 were examined, and experiments assessed tumor growth. Circ_0000467 was significantly overexpressed in CRC and associated with poor prognosis. Its upregulation enhanced tumor growth, invasion, epithelial-mesenchymal transition, and stem-like characteristics by increasing key markers (CD44, EpCAM, SOX2, and Nanog). Mechanistically, circ_0000467 acted as a molecular sponge for miR-520g, leading to increased TCF4 expression and activation of the Wnt/β-catenin pathway. Silencing TCF4 or overexpressing miR-520g reversed these effects. Circ_0000467 promotes CRC progression by regulating the TCF4/Wnt/β-catenin pathway through miR-520g, highlighting its potential as a biomarker and therapeutic target for CRC.

摘要

本研究探讨了circ_0000467在结直肠癌(CRC)进展中的作用及其作为治疗靶点的潜力。使用公开数据集和来自103例CRC患者的临床样本分析了circ_0000467的表达。功能试验评估了其对CRC细胞增殖、迁移和干细胞样特性的影响。研究了与miR-520g和TCF4的分子相互作用,并进行实验评估肿瘤生长。Circ_0000467在CRC中显著过表达,并与不良预后相关。其上调通过增加关键标志物(CD44、EpCAM、SOX2和Nanog)增强了肿瘤生长、侵袭、上皮-间质转化和干细胞样特征。机制上,circ_0000467作为miR-520g的分子海绵,导致TCF4表达增加和Wnt/β-连环蛋白通路激活。沉默TCF4或过表达miR-520g可逆转这些作用。Circ_0000467通过miR-520g调节TCF4/Wnt/β-连环蛋白通路促进CRC进展,突出了其作为CRC生物标志物和治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d876/12033044/f98c1c55cea1/ABPID9-000009-026111_1-g001.jpg

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