ArticleJournal of hematology & oncology2024
METTL16-SENP3-LTF axis confers ferroptosis resistance and facilitates tumorigenesis in hepatocellular carcinoma.
Article in Journal of hematology & oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Global research status and frontiers on ferroptosis in hepatocellular carcinoma: a comprehensive bibliometric and visualized analysis.Frontiers in immunology · 2025Pooled it
- Ferroptosis: Newly Emerged Regulator for Human Disease.MedComm · 2026Review
- OTUD1-mediated deubiquitination stabilizes SLC7A11 to suppress ferroptosis in hepatocellular carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- LINC01929 promotes breast cancer progression through a TFRC-associated ferroptosis pathway.Cell death discovery · 2026Article
- Ubiquitination and NOncology letters · 2026Review
- HAX1 Promotes Hepatocellular Carcinoma Progression by Inhibiting Ferroptosis Through Modulation of Iron Homeostasis and the GSH/GPX4 Pathway.International journal of molecular sciences · 2026Article
- Stiripentol induces ER stress and pyroptosis in pancreatic cancer cells under metabolic stress by dysregulating SFAs/UFAs homeostasis.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- METTL16 Promotes Head and Neck Squamous Cell Carcinoma Progression via m6A-Mediated Stabilization of SREBP2 mRNA and Enhanced Cholesterol Biosynthesis.Cancer medicine · 2026Article
- FAAH initiates a positive feedback loop to promote lung adenocarcinoma progression through inhibition of ferroptosis.Cell death and differentiation · 2026Article
- METTL16 promotes MASLD progression through the regulation of lipid synthesis and immune response.Biology direct · 2026Article
- Article
- RNA modifications and cancer ferroptosis.Cancer cell international · 2026Review
- SENP3 drives colorectal cancer progression by enhancing GDF15 expression.International journal of colorectal disease · 2026Article
- Ferroptosis: The dawn of reversing drug resistance in digestive cancers.Genes & diseases · 2026Review
- METTL16 in cancer: Roles and regulatory mechanisms.Genes & diseases · 2026Review
- Targeting epigenetic methylation: emerging diagnosis and therapeutic strategies in cancer.Experimental hematology & oncology · 2026Review
- Epigenetic and post-translational regulatory networks of ferroptosis in the tumor immune microenvironment.Experimental hematology & oncology · 2026Review
- Emerging insights into enhancer RNAs: biogenesis, function, mechanism, and disease implication.Briefings in bioinformatics · 2026Review
- Loss of UFL1 confers enzalutamide resistance of prostate tumors by regulating METTL16-mediated m6A modification of EEF1A1 mRNA.International journal of biological sciences · 2026Article
- LTF promotes central nervous system leukemia progression via neutrophil serine proteases.Frontiers in pharmacology · 2026Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
backgroundFerroptosis, characterized by iron-dependent lipid peroxidation, emerges as a promising avenue for hepatocellular carcinoma (HCC) intervention due to its tumor susceptibility. RNA N6-methyladenosine (m6A) modification has been involved in several types of regulated cell death. However, the roles and molecular mechanisms of m6A-related regulators in HCC cell ferroptosis remain unclear.
methodsBy examining a series of m6A modification enzymes upon ferroptosis induction or inhibition, we identified METTL16 as a novel ferroptotic repressor in HCC cells. The roles of METTL16 on ferroptosis and HCC development were investigated in multiple cell lines, human HCC organoids, subcutaneous xenografts and MYC/Trp53
resultsHigh METTL16 expression confers ferroptosis resistance in HCC cells and mouse models, and promotes cell viability and tumor progression. Mechanistically, METTL16 collaborates with IGF2BP2 to modulate SENP3 mRNA stability in an m6A-dependent manner, and the latter impedes the proteasome-mediated ubiquitination degradation of Lactotransferrin (LTF) via de-SUMOylation. Elevated LTF expression facilitates the chelation of free iron and reduces liable iron pool level. SENP3 and LTF are implicated in METTL16-mediated HCC progression and anti-ferroptotic effects both in vivo and in vitro. Clinically, METTL16 and SENP3 expression were positively correlated, and high METTL16 and SENP3 expression predicts poor prognosis in human HCC samples.
conclusionsOur study reveals a new METTL16-SENP3-LTF signaling axis regulating ferroptosis and driving HCC development. Targeting this axis is a promising strategy for sensitizing ferroptosis and against HCC.
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