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. 2025 Jun;30(5-6):1525-1546.
doi: 10.1007/s10495-025-02094-0. Epub 2025 Apr 26.

YTHDF1-mediated m6A modification promotes cisplatin resistance in ovarian cancer via the FZD7/Wnt/β-catenin pathway

Jintian Miao  1 , Xinyan Jiang  2 , Siyun Wang  2
Affiliations

YTHDF1-mediated m6A modification promotes cisplatin resistance in ovarian cancer via the FZD7/Wnt/β-catenin pathway

Jintian Miao et al. Apoptosis. 2025 Jun.

Abstract

Cisplatin resistance significantly hinders the efficacy of ovarian cancer treatment, presenting a major challenge in improving patient outcomes. This study identifies the m6A reader protein YTHDF1 as a key regulator of cisplatin resistance in ovarian cancer through its modulation of the FZD7/Wnt/β-catenin signaling pathway. Using cisplatin-resistant ovarian cancer cell lines (A2780/DDP and SKOV3/DDP), we observed elevated YTHDF1 expression, which positively correlated with tumor cell proliferation and migration. Silencing YTHDF1 reduced FZD7 expression, inhibited Wnt/β-catenin signaling, and restored cisplatin sensitivity both in vitro and in vivo. Mechanistic investigations revealed that YTHDF1 binds to m6A-modified FZD7 mRNA, enhancing its stability and translation. Functional studies in xenograft mouse models demonstrated that targeting YTHDF1 suppressed tumor growth and enhanced apoptosis in cisplatin-resistant ovarian cancer cells. These findings highlight the YTHDF1-FZD7 axis as a novel therapeutic target for overcoming cisplatin resistance, paving the way for improved treatment strategies in ovarian cancer.

Keywords: Cisplatin resistance; FZD7; Ovarian cancer; Wnt/β-catenin signaling pathway; YTHDF1.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Harbin Medical University (Approval No. SY-2019-MI-048). All animal experiments were conducted in accordance with institutional guidelines and relevant regulations. This study does not involve human participants, human data, or human tissues. Consent for publication: This study does not include individual person’s data in any form. Competing interests: The authors declare no competing interests.

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