ArticleThe Journal of biological chemistry2024
5-Methylcytosine transferase NSUN2 drives NRF2-mediated ferroptosis resistance in non-small cell lung cancer.
Article in The Journal of biological chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 35 citations in OpenAlex.
- NSUN2-FOSB reciprocity facilitates leukemogenesis in an mHaematologica · 2026Article
- RNA-Binding Peptide Influences Epitranscriptomic Regulation by Preferentially Binding to Unmodified RNAs Targeted by NSUN2.Biomolecules · 2026Article
- RNA modifications as determinants of cancer cell death: from epitranscriptomic mechanisms to therapeutic targeting.Functional & integrative genomics · 2026Review
- TRDMT1 slows lung cancer growth by stabilizing TFRC mRNA and triggering ferroptosis cell death.The Journal of biological chemistry · 2026Article
- Substrate selectivity of the human RNA mNature · 2026Article
- RNA methylation in cell death: mechanisms and clinical applications.Molecular cancer · 2026Review
- NSUN2/m5C/TPI1 axis promotes glycolysis and immune evasion in breast cancer.Journal of translational medicine · 2026Article
- Mechanism study of RUNX1/NSUN2 upregulating fatty acid-binding protein 5 through 5-methylcytosine methylation to mediate lipid metabolic reprogramming to promote immunotherapy resistance in non-small cell lung cancer.Respiratory research · 2026Article
- Epitranscriptomic control of cancer: the emerging roles of m⁵C and ac⁴C RNA modifications.Cell death discovery · 2026Review
- RNA modifications and cancer ferroptosis.Cancer cell international · 2026Review
- RNA Regulatory Networks: Key Hubs in the Panorama of Cancer and Emerging Therapeutic Targets.MedComm · 2026Review
- 5-mC RNA methylation: a key regulator in cancer development and treatment.Journal of translational medicine · 2026Review
- DUX4-induced HSATII RNA accumulation drives protein aggregation, impacting RNA processing pathways.The Journal of cell biology · 2026Article
- NSUN2 Knockdown Promotes the Ferroptosis of Colorectal Cancer Cells Via m5C Modification of SLC7A11 mRNA.Biochemical genetics · 2026Article
- The oncogenic role of NSUN2 in lung adenocarcinoma by stabilizing CCT5 mRNA via a YBX1-dependent m5C modification.Molecular and cellular biochemistry · 2026Article
- RNA Methylation in Cancer Metabolism: from Mechanisms to Therapeutic Opportunities.International journal of biological sciences · 2026Review
- Therapy-induced mRNA, rRNA and tRNA methylation alterations confer tolerance phenotype in tumor cells: mechanism and implications.International journal of biological sciences · 2026Review
- MZF1-AS1/NSUN2 promotes the peritoneal metastasis of gastric cancer by enhancing the stability of RAB13 mRNA.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- NSUNs-driven dysregulation: the next frontier in targeted cancer therapy?Cell death & disease · 2025Review
- NSUN2 Negatively Regulates TP53 mRNA Stability to Promote the Malignant Progression of Nasopharyngeal Carcinoma.Cancers · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA 5-methylcytosine (m5C) is an abundant chemical modification in mammalian RNAs and plays crucial roles in regulating vital physiological and pathological processes, especially in cancer. However, the dysregulation of m5C and its underlying mechanisms in non-small cell lung cancer (NSCLC) remain unclear. Here we identified that NSUN2, a key RNA m5C methyltransferase, is highly expressed in NSCLC tumor tissue. We found elevated NSUN2 expression levels strongly correlate with tumor grade and size, predicting poor outcomes for NSCLC patients. Furthermore, RNA-seq and subsequent confirmation studies revealed the antioxidant-promoting transcription factor NRF2 is a target of NSUN2, and depleting NSUN2 decreases the expression of NRF2 and increases the sensitivity of NSCLC cells to ferroptosis activators both in vitro and in vivo. Intriguingly, the methylated-RIP-qPCR assay results indicated that NRF2 mRNA has a higher m5C level when NSUN2 is overexpressed in NSCLC cells but shows no significant changes in the NSUN2 methyltransferase-deficient group. Mechanistically, we confirmed that NSUN2 upregulates the expression of NRF2 by enhancing the stability of NRF2 mRNA through the m5C modification within its 5'UTR region recognized by the specific m5C reader protein YBX1, rather than influencing its translation. In subsequent rescue experiments, we show knocking down NRF2 diminished the proliferation, migration, and ferroptosis tolerance mediated by NSUN2 overexpression. In conclusion, our study unveils a novel regulatory mechanism in which NSUN2 sustains NRF2 expression through an m5C-YBX1-axis, suggesting that targeting NSUN2 and its regulated ferroptosis pathway might offer promising therapeutic strategies for NSCLC patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.