Identification of m6 A-regulated ferroptosis biomarkers for prognosis in laryngeal cancer

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 14, 2025

Laryngeal cancer (LC) is a malignant tumor that occurs in the larynx. N6-methyladenosine (m6A) RNA methylation, pivotal and prevalent epigenetic modification eukaryotic mRNA, intricately intertwines with ferroptosis, together, they play crucial role development of LC. Accordingly, further research on related molecular mechanisms pathology LC necessary. Weighted gene co-expression network analysis correlation were used to identify differentially expressed m6A-related ferroptosis genes The TCGA-HNSC GSE65858 datasets obtained from public databases. dataset consisted 110 primary oropharynx samples 12 control samples, while contained forty-eight samples. Univariate Cox least absolute shrinkage selection operator (LASSO) regression utilized for feature risk model construction dataset. was validated Then, nomogram built based independent prognostic factor identified using univariate multivariate Mutation analysis, immune-related drug sensitivity prediction applied analyze utility Additionally, qRT-PCR western blot performed detect TFRC, RGS4, FTH1 expression. Three biomarkers build LASSO algorithms. Receiver operating characteristic (ROC) verified accuracy model. Tumor Immune Dysfunction Exclusion (TIDE) Estimation STromal cells MAlignant Tumors Expression data (ESTIMATE) algorithm showed positive relationship between score TIDE or ESTIMATE score. Furthermore, found 19 chemotherapy drugs strongly correlated exhibited high expression levels 30 laryngeal carcinoma tissues cell lines. Notably, TFRC significantly associated patient prognosis. In Conclusion, FTH1, as m6A-regulated LC, providing insights into treatment

Language: Английский

Artesunate induces ferroptosis in osteosarcoma through NCOA4‐mediated ferritinophagy

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(7)

Published: April 1, 2025

Abstract Osteosarcoma (OS) is a prevalent primary malignant bone tumor that lacks effective therapeutic interventions. Artesunate (ART) has been proved to have remarkable treatment effects on severe malaria and anti‐tumor properties. This study aimed investigate the anti‐OS underlying mechanisms of ART. The potential ART‐mediated activity were analyzed by using RNA sequencing, iron accumulation, lipid peroxidation, western blotting, small interfering (siRNA) transfection. In vivo, xenograft mice model was adopted explore anticancer effect present revealed ART significantly suppressed OS cell proliferation. Subsequent results suggested exerted mainly through ferroptosis pathway. decreased GSH/GSSG ratio, xCT GPX4 expression, while increasing MDA which reversed Fer‐1, DFO, 3‐MA, NCOA4 silencing. Mechanistically, upregulated expression TFR DMT1, triggered ferritinophagy upregulating NCOA4, increased Fe 2+ accumulation ferroptosis. addition, cytoplasmic further activated Mfrn2‐mediated transportation free into mitochondria, resulting in mitochondrial overload, eventually leading peroxidation Furthermore, an mouse model, administration inhibited growth Collectively, our findings indicated capacity NCOA4‐mediated ferritinophagy, might shed light future therapy.

Language: Английский

FOXM1-activated IGF2BP3 promotes cell malignant phenotypes and M2 macrophage polarization in hepatocellular carcinoma by inhibiting ferroptosis via stabilizing RRM2 mRNA in an m6A-dependent manner

Molecular and Cellular Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

Language: Английский