ArticleAging2021
miR-224 aggravates cancer-associated fibroblast-induced progression of non-small cell lung cancer by modulating a positive loop of the SIRT3/AMPK/mTOR/HIF-1α axis.
Article in Aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- SIRT3 regulates mitochondrial metabolism through deacetylation of SLC25A6 to impact gastric cancer progression and drug resistance.Journal of translational medicine · 2026Article
- Alisol A Mitigates Neuroinflammation and Oxidative Stress After Subarachnoid Hemorrhage Through SIRT3-Driven Reprogramming of Mitochondrial Metabolism.Molecular neurobiology · 2026Article
- Unraveling the molecular-pathological characteristics and cellular complexity of the tumor immune microenvironment in metastatic non-small cell lung cancer.Cell communication and signaling : CCS · 2025Review
- Sirtuin family in lung adenocarcinoma.Discover oncology · 2025Review
- Review
- miR-224 activates cancer-associated fibroblasts to enhance lung cancer cell migration and invasion by targeting Akirin1.Scientific reports · 2025Article
- Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development.Frontiers in immunology · 2025Review
- CAF-derived exosome-miR-3124-5p promotes malignant biological processes in NSCLC via the TOLLIP/TLR4-MyD88-NF-κB pathway.Oncology research · 2025Article
- Heterogeneity and interplay: the multifaceted role of cancer-associated fibroblasts in the tumor and therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Emerging role of sirtuins in non‑small cell lung cancer (Review).Oncology reports · 2024Review
- LncRNAs as nodes for the cross-talk between autophagy and Wnt signaling in pancreatic cancer drug resistance.International journal of biological sciences · 2024Review
- miRNAs Delivery for Cancer-associated Fibroblasts' Activation and Drug Resistance in Cancer Microenvironment.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Targeting sirtuins for cancer therapy: epigenetics modifications and beyond.Theranostics · 2024Review
- Mitochondrial Sirtuins in Cancer: A Revisited Review from Molecular Mechanisms to Therapeutic Strategies.Theranostics · 2024Review
- Prospects of microRNAs as therapeutic biomarkers in non-small cell lung cancer.Medical oncology (Northwood, London, England) · 2023Review
- New Perspectives on Sex Steroid Hormones Signaling in Cancer-Associated Fibroblasts of Non-Small Cell Lung Cancer.Cancers · 2023Review
- Mechanism of piR-1245/PIWI-like protein-2 regulating Janus kinase-2/signal transducer and activator of transcription-3/vascular endothelial growth factor signaling pathway in retinal neovascularization.Neural regeneration research · 2023Article
- The Role of NAD+, SIRTs Interactions in Stimulating and Counteracting Carcinogenesis.International journal of molecular sciences · 2023Review
- Cancer-associated fibroblasts in nonsmall cell lung cancer: From molecular mechanisms to clinical implications.International journal of cancer · 2022Review
- Non-coding RNAs in lung cancer: emerging regulators of angiogenesis.Journal of translational medicine · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesCancer-associated fibroblast (CAF) is among the most important tumor-host microenvironment components by affecting tumor progression. This study explored the role of miR-224 in CAF-induced non-small cell lung cancer (NSCLC). MATERIALS AND
methodsA CAF-NSCLC cell co-culture model was established, and the miR-224 expression in CAF was detected by reverse transcription-polymerase chain reaction (RT-PCR). Gain- and loss- of experiments of miR-224 were implemented to verify the effects of CAF on NSCLC cell proliferation, invasion, and epithelial-mesenchymal transition (EMT), and endothelial cell (EC) angiogenesis. Overexpressing genetic or pharmacological interventions were performed to explore the potential mechanisms of Sirtuins 3/AMP-activated protein kinase/mammalian target of rapamycin/hypoxia-inducible factor-1α (SIRT3/AMPK/mTOR/HIF-1α).
resultsCAF enhanced the malignant phenotype of NSCLC cells and induced EC angiogenesis. miR-224 was significantly altered in CAFs. miR-224 up-regulation exacerbated NSCLC development mediated by CAFs, while miR-224 inhibition mostly reversed CAF-induced effects. Mechanistically, miR-224 targeted the 3'-untranslated regions (UTR) of SIRT3 mRNA, thereby inhibiting SIRT3/AMPK and activating mTOR/HIF-1α. Forced overexpression of SIRT3 up-regulated AMPK and inactivated mTOR/HIF-1α, while inhibiting HIF-1α markedly up-regulated SIRT3/AMPK and reduced mTOR phosphorylation. Interestingly, both Sirt1 overexpression and HIF-1α inhibition repressed miR-224 levels and miR-224-mediated promotive effects in NSCLC.
conclusionThe miR-224-SIRT3/AMPK/mTOR/HIF-1α axis formed a positive feedback loop in modulating CAF-induced carcinogenic effects on NSCLC.
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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.