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METTL3 drives malignant progression in TP53-mutant prostate cancer.

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Molecular biology reports 📖 저널 OA 12.7% 2022: 1/1 OA 2023: 0/1 OA 2024: 1/5 OA 2025: 8/70 OA 2026: 10/78 OA 2022~2026 2025 Vol.53(1) p. 66
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Pu Y, Ye D, Dong N, Qin Y, Qi X

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[BACKGROUND] Prostate cancer patients harboring mutations exhibit a more aggressive and chemo-resistant phenotype.

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APA Pu Y, Ye D, et al. (2025). METTL3 drives malignant progression in TP53-mutant prostate cancer.. Molecular biology reports, 53(1), 66. https://doi.org/10.1007/s11033-025-11160-4
MLA Pu Y, et al.. "METTL3 drives malignant progression in TP53-mutant prostate cancer.." Molecular biology reports, vol. 53, no. 1, 2025, pp. 66.
PMID 41217561 ↗

Abstract

[BACKGROUND] Prostate cancer patients harboring mutations exhibit a more aggressive and chemo-resistant phenotype. Unfortunately, attempts to identify the vulnerabilities that could be exploited to overcome these aggressive malignancies have made only minimal progress in recent years. Consequently, there is an immediate requirement to investigate novel therapeutic strategies for this subclass. METTL3 complex, knowing to govern m6A dynamic alteration, has been suggested to be a critical therapeutic target across human cancer. However, the role of METTL3 in prostate cancer harboring mutations is totally unknown.

[MATERIALS AND METHODS] Bioinformatic analysis was employed to assess the transcriptome signature between and prostate cancer and the expression of METTL3 complex in and prostate cancer. Colony formation and growth curve analyses were employed to assess the role of METTL3 in prostate cancer. Furthermore, the bioinformatic analyses were utilized for uncovering the underlying mechanism of how METTL3 maintained the malignancy phenotype of prostate cancer.

[RESULTS] as one of the most frequently mutated genes in prostate cancer. Transcriptome analysis revealed that mutation significantly downregulated genes associated with prohibiting proliferation. Moreover, the core catalytic subunit, METTL3, was found to be aberrantly upregulated in TP53 mutated prostate cancer compared to that in normal and prostate tissues. Notably, pharmaceutically blockade of METTL3 drastically inhibited mutated prostate cancer cells growth. Bioinformatic analysis suggested that METTL3 inhibition maintained mutated prostate cancer malignancies via activating MAPK signaling.

[CONCLUSIONS] METTL3 serves as a novel targetable vulnerability for prostate cancer. Targeting METTL3 prohibits the mutated prostate cancer growth by inactivating MAPK signaling.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s11033-025-11160-4.

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