CircZFR/YTHDF3 axis drives lymph node metastasis in cervical cancer via FASN translation

IF 33.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2025-08-21 DOI:10.1186/s12943-025-02424-5

Mingyi Zhou, Yan Gao, Yong Zhang, Lian He, Bo Gao, Yue Zhang, Francois X. Claret, George A. Calin, Danbo Wang

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引用次数: 0

Abstract

Lymph node metastasis is a key driver of poor outcomes in cervical cancer. However, the molecular mechanisms of circular RNAs (circRNAs) driving cervical cancer lymph node metastasis remain unclear. We identified circZFR, fatty acid synthase (FASN) and YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) protein expression in the cervical cancer patients with long and short disease-free survival (DFS). Functional experiments were performed to investigate the function of circZFR, FASN and YTHDF3 on cell migration and invasion. MeRIP-qPCR, RNA pulldown, RNA Immunoprecipitation (RIP), and Co-Immunoprecipitation (Co-IP) assays were executed to investigate the mechanism of circZFR regulating FASN protein expression. Our study reveals that elevated FASN protein is closely linked to metastasis and reduced survival, and identified a regulatory mechanism involving circular RNAs. We identified circZFR as a crucial regulator, significantly enhancing FASN protein expression. CircZFR overexpression was significantly correlated with accelerated lymph node metastasis and shortened DFS. Mechanistically, circZFR binds to the m6A reader protein YTHDF3, facilitating m6A recognition on FASN mRNA and recruiting the translation initiator eIF4A3, thereby boosting FASN translation. These findings establish circZFR as a pivotal driver of cervical cancer progression and highlight its inhibition as a promising therapeutic strategy.

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CircZFR/YTHDF3轴通过FASN翻译驱动宫颈癌淋巴结转移

淋巴结转移是宫颈癌预后不良的关键驱动因素。然而，环状rna （circRNAs）驱动宫颈癌淋巴结转移的分子机制尚不清楚。我们检测了circZFR、脂肪酸合成酶（FASN）和YTH n6 -甲基腺苷RNA结合蛋白F3 （YTHDF3）蛋白在宫颈癌长、短无病生存期（DFS）患者中的表达。通过功能实验研究circZFR、FASN和YTHDF3对细胞迁移和侵袭的作用。采用MeRIP-qPCR、RNA pull - down、RNA Immunoprecipitation （RIP）、Co-Immunoprecipitation （Co-IP）等方法研究circZFR调控FASN蛋白表达的机制。我们的研究表明，FASN蛋白的升高与转移和生存降低密切相关，并确定了一个涉及环状rna的调控机制。我们发现circZFR是一个关键的调节因子，显著增强FASN蛋白的表达。CircZFR过表达与淋巴结转移加速、DFS缩短显著相关。机制上，circZFR与m6A读取器蛋白YTHDF3结合，促进FASN mRNA对m6A的识别，招募翻译启动子eIF4A3，从而促进FASN翻译。这些发现表明circZFR是宫颈癌进展的关键驱动因素，并强调其抑制是一种有前景的治疗策略。

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

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

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