N6-methyladenosine-mediated EIF3H promotes anaplastic thyroid cancer progression and ferroptosis resistance by stabilizing β-catenin.

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Tác giả: Xinying Li, Xiangyuan Qiu, Fada Xia, Zeyu Zhang, Di Zhou

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : Free radical biology & medicine , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 702633

Anaplastic thyroid cancer (ATC) patients suffer from a poor prognosis with very limited treatment options. The accumulation of β-catenin and the activation of downstream signaling is one of the main events in ATC, while the role of JAMM family in ATC remains unknown. In this study, we aimed to identify a new deubiquitinating enzyme regulating β-catenin in ATC. We found that EIF3H was positively correlated with β-catenin, and the knockdown of EIF3H deactivated the Wnt/β-catenin signaling pathway in ATC. Further exploration revealed that EIF3H interacted with, deubiquitylated, and stabilized β-catenin by acting as a deubiquitinating enzyme. Mechanistically, EIF3H removed the K48-linked ubiquitin chain on β-catenin by binding the N tails of β-catenin. The knockdown of EIF3H could inhibit ATC cell proliferation, invasion, and ferroptosis resistance by regulating β-catenin. In addition, the dysregulation of EIF3H was associated with m6A modification in the 3'UTR and a m6A reader, IGF2BP2. In summary, the EIF3H/β-catenin axis promotes ATC progression and ferroptosis resistance by activating the Wnt/β-catenin signaling pathway. The EIF3H/β-catenin axis may serve as a potential diagnostic marker and a therapeutic target in ATC.
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