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. 2025 Jun 10.
doi: 10.1007/s12013-025-01794-3. Online ahead of print.

Bladder Cancer Growth is Inhibited by Upregulating CircFUT8 through the METTL14/FMR1 Signaling Pathway

Weifeng Yang #  1   2 , Jinhui Zha #  3 , Youjuan Tang #  4 , Kebing Wang  5 , Haitian He  5 , Can Zeng  5 , Yang Wang  5 , Xiaoyong Yu  3 , Zeshen Wu  3 , Shiheng He  3
Affiliations

Bladder Cancer Growth is Inhibited by Upregulating CircFUT8 through the METTL14/FMR1 Signaling Pathway

Weifeng Yang et al. Cell Biochem Biophys. .

Abstract

Bladder cancer (BCa) is one of the most common malignancies worldwide. This study investigates the role of the N6-methyladenosine (m6A)/circRNA regulatory axis in BCa tumor growth and elucidates its underlying molecular mechanisms. A total of 15 paired BCa and adjacent non-tumor tissues were collected. CircFUT8 expression was found to be significantly downregulated in BCa tissues and exhibited a positive correlation with methyltransferase-like 14 (METTL14) levels. It could also undergo m6A methylation, its expression was significantly upregulated following METTL14 overexpression in both T24 and UM-UC-3 cells, and silencing circFUT8 counteracted the suppressive effects of METTL14 overexpression on BCa cell growth and migration. RNA immunoprecipitation (RIP) assays confirmed that circFUT8 interacted with fragile X mental retardation 1 (FMR1), and FMR1 overexpression enhanced circFUT8 expression, while FMR1 knockdown diminished the effects of circFUT8 overexpression. In mice, FMR1 overexpression led to elevated circFUT8 levels, reduced Ki67 expression and smaller tumor volumes, and these effects could be reversed following METTL14 knockdown. Collectively, these findings highlight the METTL14/FMR1 signaling axis could enhance circFUT8 expression to inhibit BCa cells growth and migration. CircFUT8 thus represents a promising target for therapeutic intervention and provides novel mechanistic insights into the epigenetic regulation of BCa progression.

Keywords: Bladder cancer; CircFUT8; FMR1; M6A; METTL14.

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Conflict of interest statement

Compliance with Ethical Standards. Conflict of Interest: The authors declare no competing interests. Ethics Approval: The study was approved by Ethics Committee of Qianhai Shekou Free Trade Zone Hospital (2023KY-004-01K). All methods were carried out in accordance with relevant guidelines and regulations. Informed Consent: Written informed consent was obtained from each patient.

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