Trial reportSignal transduction and targeted therapy2022
LncRNAs LCETRL3 and LCETRL4 at chromosome 4q12 diminish EGFR-TKIs efficiency in NSCLC through stabilizing TDP43 and EIF2S1.
Trial report in Signal transduction and targeted therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
What it found
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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
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- The prognostic significance of lncRNA FGD5-AS1 in various malignancies: a meta-analysis.Frontiers in oncology · 2024Pooled it
- Prognostic effect of lncRNA BBOX1-AS1 in malignancies: a meta-analysis.Frontiers in genetics · 2023Pooled it
- Male germ cell-specific deletion ofZoological research · 2026Article
- LINC00973/DTX3L Axis Promotes Non-Small Cell Lung Cancer Progression and Serves as a Therapeutic Target.Smart medicine · 2026Article
- Dual relevance ofFrontiers in oncology · 2026Article
- Long non-coding RNAs in cancer glycolysis and metabolism: mechanisms and translational opportunities.Cell death & disease · 2025Review
- Mechanistic Insights and Therapeutic Potentials of Ubiquitin-Proteasome System in Non-Small Cell Lung Cancer.Cell proliferation · 2025Review
- "Molecular pigeon" network of lncRNA and miRNA: decoding metabolic reprogramming in patients with lung cancer.Frontiers in oncology · 2025Review
- Decoding TDP-43: the molecular chameleon of neurodegenerative diseases.Acta neuropathologica communications · 2024Review
- The TDP-43/TP63 Positive Feedback Circuit Promotes Esophageal Squamous Cell Carcinoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury.BMC cardiovascular disorders · 2024Article
- Comprehensive landscape and future perspective of long noncoding RNAs in non-small cell lung cancer: it takes a village.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Implications of TDP-43 in non-neuronal systems.Cell communication and signaling : CCS · 2023Review
- TDP-43 Epigenetic Facets and Their Neurodegenerative Implications.International journal of molecular sciences · 2023Review
- LINC02159 promotes non-small cell lung cancer progression via ALYREF/YAP1 signaling.Molecular cancer · 2023Article
- Circ_0087378 intensifies the malignant behavior of non-small cell lung cancer cellsTranslational lung cancer research · 2023Article
- LINC00240 in the 6p22.1 risk locus promotes gastric cancer progression through USP10-mediated DDX21 stabilization.Journal of experimental & clinical cancer research : CR · 2023Article
- Long non-coding RNAs in non-small cell lung cancer: implications for EGFR-TKI resistance.Frontiers in genetics · 2023Review
- YAP1 as a Novel Negative Biomarker of Immune Checkpoint Inhibitors for EGFR-Mutant Non-Small-Cell Lung Cancer.Canadian respiratory journal · 2023Article
- Hub Genes in Non-Small Cell Lung Cancer Regulatory Networks.Biomolecules · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are effective targeted therapy drugs for advanced non-small cell lung cancer (NSCLC) patients carrying sensitized EGFR mutations. The rapid development of EGFR-TKIs resistance represents a major clinical challenge for managing NSCLC. The chromosome 4q12 is the first genome-wide association study (GWAS)-reported locus associated with progression-free survival (PFS) of NSCLC patients treated with EGFR-TKIs. However, the biological significance of the noncoding transcripts at 4q12 in NSCLC remains elusive. In the present study, we identified two 4q12 long noncoding RNAs (lncRNAs) LCETRL3 and LCETRL4 which could significantly dimmish EGFR-TKIs efficiency. In line with their oncogenic role, evidently higher LCETRL3 and LCETRL4 levels were observed in NSCLC tissues as compared with normal specimens. Importantly, lncRNA LCETRL3 can interact with oncoprotein TDP43 and inhibit ubiquitination and degradation of TDP43. Similarly, lncRNA LCETRL4 can bind and stabilize oncoprotein EIF2S1 through reducing ubiquitin-proteasome degradation of EIF2S1. In particular, elevated levels of LCETRL3 or LCETRL4 in NSCLC cells resulted in stabilization of TDP43 or EIF2S1, increased levels of NOTCH1 or phosphorylated PDK1, activated AKT signaling and, thus, EGFR-TKIs resistance. Taken together, our data revealed a novel model that integrates two lncRNAs transcribed from the 4q12 locus into the regulation of EGFR-TKIs resistance in NSCLC. These findings shed new light on the importance of functionally annotating lncRNAs in the GWAS loci and provided insights to declare novel druggable targets, i.e., lncRNAs, which may unlock the therapeutic potential of EGFR-TKIs resistant NSCLC in the clinic.
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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 Socratic graph.