ArticleScience advances2024
Treatment with siRNAs is commonly associated with GPX4 up-regulation and target knockdown-independent sensitization to ferroptosis.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 17 citations in OpenAlex.
- Metabolic rewiring driven by phosphoglycolate phosphatase deletion inhibits ferroptosis.Science advances · 2026Article
- Dual lipid modulation overcomes ferroptosis resistance in high-risk neuroblastoma.Cell death and differentiation · 2026Article
- KIF11 prevents retinal endothelial ferroptosis in familial exudative vitreoretinopathy by inhibiting phosphorylation-driven PRDX1 phase separation.Nature communications · 2026Article
- Tumour acidosis remodels the glycocalyx to control lipid scavenging and ferroptosis.Nature cell biology · 2026Article
- Old dogs-new tricks: multifaceted functions of MAVS beyond antivirus activity in human health and diseases.Cell & bioscience · 2025Review
- Coenzyme A protects against ferroptosis via CoAlation of mitochondrial thioredoxin reductase.The Journal of clinical investigation · 2025Article
- STX17-DT facilitates axitinib resistance in renal cell carcinoma by inhibiting mitochondrial ROS accumulation and ferroptosis.Cell death & disease · 2025Article
- Targeting ferroptosis to enhance the efficacy of mesenchymal stem cell-based treatments for intervertebral disc degeneration.International journal of biological sciences · 2025Review
- Regulated cell death and DAMPs as biomarkers and therapeutic targets in normothermic perfusion of transplant organs. Part 1: their emergence from injuries to the donor organ.Frontiers in transplantation · 2025Review
- Corneal Mucin-Targeting Liposome Nanoplatforms Enable Effective Treatment of Dry Eye Diseases by Integrated Regulation of Ferroptosis and Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Therapeutic induction of ferroptosis in tumors using PD-L1 targeting antibody nanogel conjugates.Cell chemical biology · 2024Article
- Integration of epigenomic and transcriptomic profiling uncovers EZH2 target genes linked to cysteine metabolism in hepatocellular carcinoma.Cell death & disease · 2024Article
- Ferroptosis-based advanced therapies as treatment approaches for metabolic and cardiovascular diseases.Cell death and differentiation · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small interfering RNAs (siRNAs) are widely used in biomedical research and in clinical trials. Here, we demonstrate that siRNA treatment is commonly associated with significant sensitization to ferroptosis, independently of the target protein knockdown. Genetically targeting mitochondrial antiviral-signaling protein (MAVS) reversed the siRNA-mediated sensitizing effect, but no activation of canonical MAVS signaling, which involves phosphorylation of IkBα and interferon regulatory transcription factor 3 (IRF3), was observed. In contrast, MAVS mediated a noncanonical signal resulting in a prominent increase in mitochondrial ROS levels, and increase in the BACH1/pNRF2 transcription factor ratio and GPX4 up-regulation, which was associated with a 50% decrease in intracellular glutathione levels. We conclude that siRNAs commonly sensitize to ferroptosis and may severely compromise the conclusions drawn from silencing approaches in biomedical research. Finally, as ferroptosis contributes to a variety of pathophysiological processes, we cannot exclude side effects in human siRNA-based therapeutical concepts that should be clinically tested.
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.