ArticleCell death discovery2024
NEAT1_1 confers gefitinib resistance in lung adenocarcinoma through promoting AKR1C1-mediated ferroptosis defence.
Article in Cell death discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 33 citations in OpenAlex.
- Therapeutic resistance in cancer: lncRNAs as modulators and targets for cancer therapy.Genes & diseases · 2026Review
- LINC01446/miR-338-3p/APEX1 Axis Promotes Ferroptosis Defense and Progression in Esophageal Squamous Cell Carcinoma.Cancers · 2026Article
- Macrophage Notch1 drives hepatocyte ferroptosis via the exosomal miR-142a-3p/TIPE2 axis to promote MASH progression.Cell & bioscience · 2026Article
- NEAT1: a multifaceted long non-coding RNA in multiple myeloma.Haematologica · 2026Review
- Multi-algorithm machine learning combined with in silico gene knockout reveals the diagnostic value and functional regulatory networks of ferroptosis-related genes in gastric cancer.Translational cancer research · 2026Article
- Genetic mutations governing ferroptosis sensitivity and resistance: a precision approach to cancer therapy.Cell death & disease · 2026Review
- Targeting AKR1C1 overcomes lenvatinib resistance in hepatocellular carcinoma through the STAT3-ABC transporters pathway.Journal of gastrointestinal oncology · 2026Article
- The Oncogenic Role of Long Non-Coding RNABiology · 2026Review
- FN-1501 Synergistically Enhances Almonertinib Efficacy in EGFR-TKI-Resistant Lung Adenocarcinoma through Ferroptosis Induction.Anti-cancer agents in medicinal chemistry · 2026Article
- Role of Aldo-Keto reductase family 1 member C in cancer progression: a special focus on the role of AKR1C1 in pancreatic cancer.Medical oncology (Northwood, London, England) · 2025Article
- The intersection of ferroptosis and non-coding RNAs: a novel approach to lung cancer.Irish journal of medical science · 2025Review
- Insights into organelle forming RNAs: Diversity, functions and future perspectives.Animal models and experimental medicine · 2025Review
- Article
- [Layered double hydroxide-loaded si-NEAT1 regulates paclitaxel resistance and tumor-associated macrophage polarization in breast cancer by targeting miR-133b/PD-L1].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- SOX4 promotes triple-negative breast cancer progression by promoting SRPX2 transcription to regulate AKR1C1.Journal of molecular histology · 2025Article
- Ferroptosis-related LncRNAs in diseases.BMC biology · 2025Review
- U2AF65 mediated circPVT1 promotes NSCLC cell proliferation and inhibits ferroptosis through the miR-338-3p/GPX4 axis.Cell biology and toxicology · 2025Article
- On QSPR analysis of pulmonary cancer drugs using python-driven topological modeling.Scientific reports · 2025Article
- The Intricate Web of MicroRNAs in Modulating EGFR-TKI Resistance in Non-Small Cell Lung Cancer: A Comprehensive Review.Cancer management and research · 2025Review
- Non‑coding RNA‑mediated epigenetic modification of ferroptosis in non‑small cell lung cancer (Review).International journal of oncology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Gefitinib is one of the most extensively utilized epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for treating advanced lung adenocarcinoma (LUAD) patients harboring EGFR mutation. However, the emergence of drug resistance significantly compromised the clinical efficacy of EGFR-TKIs. Gaining further insights into the molecular mechanisms underlying gefitinib resistance holds promise for developing novel strategies to overcome the resistance and improve the prognosis in LUAD patients. Here, we identified that the inhibitory efficacy of gefitinib on EGFR-mutated LUAD cells was partially dependent on the induction of ferroptosis, and ferroptosis protection resulted in gefitinib resistance. Among the ferroptosis suppressors, aldo-keto reductase family 1 member C1 (AKR1C1) exhibited significant upregulation in gefitinib-resistant strains of LUAD cells and predicted poor progression-free survival (PFS) and overall survival (OS) of LUAD patients who received first-generation EGFR-TKI treatment. Knockdown of AKR1C1 partially reversed drug resistance by re-sensitizing the LUAD cells to gefitinib-mediated ferroptosis. The decreased expression of miR-338-3p contributed to the aberrant upregulation of AKR1C1 in gefitinib-resistant LUAD cells. Furthermore, upregulated long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1_1 (NEAT1_1) sponged miR-338-3p to neutralize its suppression on AKR1C1. Dual-luciferase reporter assay and miRNA rescue experiment confirmed the NEAT1_1/miR-338-3p/AKR1C1 axis in EGFR-mutated LUAD cells. Gain- and loss-of-function assays demonstrated that the NEAT1_1/miR-338-3p/AKR1C1 axis promoted gefitinib resistance, proliferation, migration, and invasion in LUAD cells. This study reveals the effects of NEAT1_1/miR-338-3p/AKR1C1 axis-mediated ferroptosis defence in gefitinib resistance in LUAD. Thus, targeting NEAT1_1/miR-338-3p/AKR1C1 axis might be a novel strategy for overcoming gefitinib resistance in LUAD harboring EGFR mutation.
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.