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The m6A Reader YTHDF1 Promotes Lung Carcinoma Progression via Regulating Ferritin Mediate Ferroptosis in an m6A-Dependent Manner

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机构: [1]Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China [2]Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangzhou 510006, China [3]Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
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关键词: lung cancer YTHDF1 N6-methyladenosine (m6A) modification ferroptosis ferritin

摘要:
N6-methyladenosine (m6A) plays a significant role as an epigenetic mechanism, which is involved in various cancers' progress via regulating mRNA modification. As a crucial m6A "reader", YTHDF1 is able to alter m6A-modified mRNA and promote the protein translation process in multiple cancers. However, the role of YTHDF1 in lung cancer has not been fully investigated. This study focuses on elucidating the function of YTHDF1 in the development of lung cancer and its underlying mechanism. We demonstrated that YTHDF1 was highly expressed in lung carcinoma progression; then, the loss of function experiments in lung cell lines confirmed that knockdown of YTHDF1 suppressed cell proliferation, migration and invasion and induced ferroptosis of lung cancer cells. Further functional assays showed that ferritin (FTH) was identified as the key target of YTHDF1 in lung cancer cells. Furthermore, the overexpression of ferritin in YTHDF1-depleted cells partially restored lung cancer cell suppression. Collectively, our data suggested that the upregulation of YTHDF1 promotes lung cancer carcinogenesis by accelerating ferritin translation in an m6A-dependent manner. We hope that our findings may provide a new target for lung cancer diagnosis and treatment.

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出版当年[2022]版:
大类 | 3 区 医学
小类 | 3 区 药学 3 区 药物化学
最新[2025]版:
大类 | 3 区 医学
小类 | 2 区 药学 3 区 药物化学
第一作者:
第一作者机构: [1]Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China [2]Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangzhou 510006, China
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通讯机构: [1]Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China [2]Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangzhou 510006, China
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