ArticleNature2013
EGFR modulates microRNA maturation in response to hypoxia through phosphorylation of AGO2.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 227 papers, 1 of them a synthesis that pooled it.
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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
227 citing papers in PubMed, 1 synthesis or guideline pooled it, 355 citations in OpenAlex.
- Diagnostic value of microRNAs in asbestos exposure and malignant mesothelioma: systematic review and qualitative meta-analysis.Oncotarget · 2016Pooled it
- Kinase regulation of miRNA networks in cardiometabolic disease: emerging pathways to precision therapy.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Regulation of epidermal growth factor receptors: The role of c-Cbl, Cdc42, and miRNAs in breast cancer.Biochemistry and biophysics reports · 2026Review
- Article
- Targeting the TRIM25-AGO2-miR-148b-5p-ABCC1 axis overcomes chemoresistance in non-small cell lung cancer.Cell death & disease · 2026Article
- From EGFR PTM network to TKI resistance: spatial subtypes and targeting in lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Partners in Silencing: Decoding the Mammalian Argonaute Interactome.Non-coding RNA · 2025Review
- Exploring Multi-Target Therapeutic Strategies for Glioblastoma via Endogenous Network Modeling.International journal of molecular sciences · 2025Article
- Predictive value of circulating microRNA-21 levels in patients with advanced non-small cell lung cancer treated with immunotherapy.Ecancermedicalscience · 2025Article
- PCBP2-dependent secretion of miRNAs via extracellular vesicles contributes to the EGFR-driven angiogenesis.Theranostics · 2025Article
- Recent Advances in the miRNA-Mediated Regulation of Neuronal Differentiation and Death.Neuromolecular medicine · 2024Review
- The Role of Dicer Phosphorylation in Gemcitabine Resistance of Pancreatic Cancer.International journal of molecular sciences · 2024Article
- Loss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference.Nucleic acids research · 2024Article
- Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma.Cellular and molecular life sciences : CMLS · 2024Article
- Beyond genetics: driving cancer with the tumour microenvironment behind the wheel.Nature reviews. Cancer · 2024Review
- Phosphorylation of AGO2 by TBK1 Promotes the Formation of Oncogenic miRISC in NSCLC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Next-Cell Hypothesis: Mechanism of Obesity-Associated Carcinogenesis.Advances in experimental medicine and biology · 2024Review
- Article
- AGO2 silences mobile transposons in the nucleus of quiescent cells.Nature structural & molecular biology · 2023Article
- Casein kinase 1 and 2 phosphorylate Argonaute proteins to regulate miRNA-mediated gene silencing.EMBO reports · 2023Article
167 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
MicroRNAs (miRNAs) are generated by two-step processing to yield small RNAs that negatively regulate target gene expression at the post-transcriptional level. Deregulation of miRNAs has been linked to diverse pathological processes, including cancer. Recent studies have also implicated miRNAs in the regulation of cellular response to a spectrum of stresses, such as hypoxia, which is frequently encountered in the poorly angiogenic core of a solid tumour. However, the upstream regulators of miRNA biogenesis machineries remain obscure, raising the question of how tumour cells efficiently coordinate and impose specificity on miRNA expression and function in response to stresses. Here we show that epidermal growth factor receptor (EGFR), which is the product of a well-characterized oncogene in human cancers, suppresses the maturation of specific tumour-suppressor-like miRNAs in response to hypoxic stress through phosphorylation of argonaute 2 (AGO2) at Tyr 393. The association between EGFR and AGO2 is enhanced by hypoxia, leading to elevated AGO2-Y393 phosphorylation, which in turn reduces the binding of Dicer to AGO2 and inhibits miRNA processing from precursor miRNAs to mature miRNAs. We also identify a long-loop structure in precursor miRNAs as a critical regulatory element in phospho-Y393-AGO2-mediated miRNA maturation. Furthermore, AGO2-Y393 phosphorylation mediates EGFR-enhanced cell survival and invasiveness under hypoxia, and correlates with poorer overall survival in breast cancer patients. Our study reveals a previously unrecognized function of EGFR in miRNA maturation and demonstrates how EGFR is likely to function as a regulator of AGO2 through novel post-translational modification. These findings suggest that modulation of miRNA biogenesis is important for stress response in tumour cells and has potential clinical implications.
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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 OpenQuestion graph.