N6-methyadenosine-modified YWHAE mRNA promotes proliferation and inhibits ferroptosis in hepatoblastoma by mediating SLC7A11 expression.

IF 6.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Oncogene Pub Date : 2025-03-12 DOI:10.1038/s41388-025-03334-y

Jiquan Zhou, Jing Wang, Liyuan Yang, Tingyi Fu, Hui Li, Yuhua Shan, Hongxiang Gao, Chenjie Xie, Lei Zhang, Min Zhang, Ji Ma, Li Liu, Houshun Fang, Dapeng Jiang, Min Xu, Qiuhui Pan, Song Gu

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引用次数: 0

Abstract

Hepatoblastoma (HB) is a rare but predominant liver cancer in children, with few treatment choices in advanced stages. YWHAE is closely related to several human diseases and acts as a molecular scaffold for malignant transformation. However, whether YWHAE promotes HB development remains unknown. Conducting RNA and m⁶A sequencing on HB tissues, we found that YWHAE was upregulated and modified by N6-methyadenosine. Functionally, YWHAE promoted proliferation and inhibited cell death in HB by in vitro and in vivo studies. Mechanistically, METTL3-dependent m⁶A modification activated YWHAE mRNA expression, and the m⁶A reader IGF2BP2 recognized and bound to the m⁶A site on YWHAE mRNA, thereby enhancing the mRNA stability of YWHAE. Interestingly, RNA sequencing revealed that YWHAE knockdown was involved in regulating ferroptosis of HB cells by mediating SLC7A11 expression. Moreover, knockdown of YWHAE significantly increased the levels of lipid ROS and peroxides in HB cells, promoting the susceptibility of HB cells to ferroptosis. In summary, these findings illuminated the role of YWHAE in HB progression and uncovered its relevance to ferroptosis as a new therapeutic target for HB.

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来源期刊

Oncogene 医学-生化与分子生物学

CiteScore

15.30

自引率

1.20%

发文量

404

审稿时长

1 months

期刊介绍： Oncogene is dedicated to advancing our understanding of cancer processes through the publication of exceptional research. The journal seeks to disseminate work that challenges conventional theories and contributes to establishing new paradigms in the etio-pathogenesis, diagnosis, treatment, or prevention of cancers. Emphasis is placed on research shedding light on processes driving metastatic spread and providing crucial insights into cancer biology beyond existing knowledge. Areas covered include the cellular and molecular biology of cancer, resistance to cancer therapies, and the development of improved approaches to enhance survival. Oncogene spans the spectrum of cancer biology, from fundamental and theoretical work to translational, applied, and clinical research, including early and late Phase clinical trials, particularly those with biologic and translational endpoints.