METTL7B-Mediated m6A Modification of PLEKHA4 Suppresses Ferroptosis via Reducing AURKA Ubiquitination to Promote Papillary Thyroid Cancer Progression.
4 affiliations
- 1Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
- 2Department of General Surgery, Second Division, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
- 3First Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China.
- 4Fujian Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Abstract
The malignant progression of papillary thyroid carcinoma (PTC) is closely associated with the acquisition of ferroptosis resistance by tumor cells; however, the upstream regulatory mechanisms remain poorly understood. This study aims to elucidate the function and molecular mechanisms of the methyltransferase-like 7B (METTL7B)/pleckstrin homology domain-containing family A member 4 (PLEKHA4)/aurora kinase A (AURKA) signaling axis in ferroptosis resistance in PTC. Our results showed that PLEKHA4 was highly expressed in PTC. By binding to kelch-like protein 12 (KLHL12), PLEKHA4 inhibited KLHL12-mediated ubiquitination and degradation of AURKA, thereby stabilizing the AURKA protein and enhancing ferroptosis resistance in PTC cells. Upstream, METTL7B stabilized PLEKHA4 mRNA and upregulated its expression through N6-methyladenosine (m6A) modification. Both in vitro and in vivo experiments confirmed that knockdown of METTL7B increased ferroptosis sensitivity and suppressed PTC progression. This study reveals a novel paradigm in which PLEKHA4, as an effector of m6A modification, regulates ferroptosis by interfering with ubiquitin-mediated degradation, providing a theoretical basis for targeting this pathway in the treatment of PTC.
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BibTeX
@article{lin2026mettl7bmediated,
title = {{METTL7B-Mediated m6A Modification of PLEKHA4 Suppresses Ferroptosis via Reducing AURKA Ubiquitination to Promote Papillary Thyroid Cancer Progression.}},
author = {Wei Lin and Kunlin Wu and Jinshu Chen and Zhaomei Yu and Huihao Zhang and Xiangjin Chen},
journal = {Cancer medicine},
year = {2026},
month = oct,
doi = {10.1002/cam4.72373},
url = {https://europepmc.org/article/MED/42952102},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - METTL7B-Mediated m6A Modification of PLEKHA4 Suppresses Ferroptosis via Reducing AURKA Ubiquitination to Promote Papillary Thyroid Cancer Progression.
AU - Wei Lin
AU - Kunlin Wu
AU - Jinshu Chen
AU - Zhaomei Yu
AU - Huihao Zhang
AU - Xiangjin Chen
PY - 2026
DA - 2026/10/28
JO - Cancer medicine
DO - 10.1002/cam4.72373
UR - https://europepmc.org/article/MED/42952102
AB - The malignant progression of papillary thyroid carcinoma (PTC) is closely associated with the acquisition of ferroptosis resistance by tumor cells; however, the upstream regulatory mechanisms remain poorly understood. This study aims to elucidate the function and molecular mechanisms of the methyltransferase-like 7B (METTL7B)/pleckstrin homology domain-containing family A member 4 (PLEKHA4)/aurora kinase A (AURKA) signaling axis in ferroptosis resistance in PTC. Our results showed that PLEKHA4 was highly expressed in PTC. By binding to kelch-like protein 12 (KLHL12), PLEKHA4 inhibited KLHL12-mediated ubiquitination and degradation of AURKA, thereby stabilizing the AURKA protein and enhancing ferroptosis resistance in PTC cells. Upstream, METTL7B stabilized PLEKHA4 mRNA and upregulated its expression through N6-methyladenosine (m6A) modification. Both in vitro and in vivo experiments confirmed that knockdown of METTL7B increased ferroptosis sensitivity and suppressed PTC progression. This study reveals a novel paradigm in which PLEKHA4, as an effector of m6A modification, regulates ferroptosis by interfering with ubiquitin-mediated degradation, providing a theoretical basis for targeting this pathway in the treatment of PTC.
SN - 2045-7634
ER -