ArticleJournal of translational medicine2024
Single-cell transcriptomic sequencing data reveal aberrant DNA methylation in SMAD3 promoter region in tumor-associated fibroblasts affecting molecular mechanism of radiosensitivity in non-small cell lung cancer.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 17 citations in OpenAlex.
- HDAC1 promotes lung adenocarcinoma progression via the nuclear accumulation of β‑catenin.Oncology reports · 2026Article
- A Non-Canonical Core Transcriptional Regulatory Circuit Orchestrates Chromatin Reprogramming to Drive Osimertinib Resistance in Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Single-nucleus sequencing dissects the malignant change of early lung adenocarcinoma: SMAD3 suppresses antitumor T cell immunity via ICAM1.NPJ precision oncology · 2026Article
- Coordinated Multicellular Immune Programs and Drug Targets Revealed by Single-Cell Analysis in Driver-Mutated NSCLC.International journal of molecular sciences · 2026Article
- Translating tumor epigenetic subtyping into methylome network-based prognostic models in early-stage NSCLC: results from the prospective MOBIT study.Journal of translational medicine · 2026Article
- Cancer-associated fibroblasts: enablers of tumor drug resistance.Journal of translational medicine · 2026Review
- Construction of a novel radioresistance-related signature for prediction of prognosis, immune microenvironment and anti-tumour drug sensitivity in non-small cell lung cancer.Annals of medicine · 2025Article
- Identification of ALDH7A1 as a DNA-methylation-driven gene in lung squamous cell carcinoma.Annals of medicine · 2025Article
- Research trends in epigenetic studies on lung cancer: a bibliometric and visual analysis of the past decade.Journal of thoracic disease · 2025Article
- Significance of Epigenetic Alteration in Cancer-Associated Fibroblasts on the Development of Carcinoma.International journal of molecular sciences · 2025Review
- STAT1 increases the sensitivity of lung adenocarcinoma to carbon ion irradiation via HO-1-mediated ferroptosis.Molecular and cellular biochemistry · 2025Article
- Cancer‑associated fibroblasts: a pivotal regulator of tumor microenvironment in the context of radiotherapy.Cell communication and signaling : CCS · 2025Review
- Profiles of Circulating Exosomal miRNA in Patients with SAPHO Patients by High-Throughput Sequencing.Combinatorial chemistry & high throughput screening · 2025Article
- Epigenetic regulation of the tumor microenvironment in lung cancer: mechanism insights and therapeutic prospects.Frontiers in immunology · 2025Review
- Cancer-associated fibroblasts, tumor and radiotherapy: interactions in the tumor micro-environment.Journal of experimental & clinical cancer research : CR · 2024Review
- Identification of SLC22A17 DNA methylation hotspot as a potential biomarker in cutaneous melanoma.Journal of translational medicine · 2024Article
- TGM2-Mediated Autophagy Contributes to the Radio-Resistance of Non-Small Cell Lung Cancer Stem-like Cells.Biomedicines · 2024Article
- The complex interplay of tumor-infiltrating cells in driving therapeutic resistance pathways.Cell communication and signaling : CCS · 2024Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveNon-small cell lung cancer (NSCLC) often exhibits resistance to radiotherapy, posing significant treatment challenges. This study investigates the role of SMAD3 in NSCLC, focusing on its potential in influencing radiosensitivity via the ITGA6/PI3K/Akt pathway.
methodsThe study utilized gene expression data from the GEO database to identify differentially expressed genes related to radiotherapy resistance in NSCLC. Using the GSE37745 dataset, prognostic genes were identified through Cox regression and survival analysis. Functional roles of target genes were explored using Gene Set Enrichment Analysis (GSEA) and co-expression analyses. Gene promoter methylation levels were assessed using databases like UALCAN, DNMIVD, and UCSC Xena, while the TISCH database provided insights into the correlation between target genes and CAFs. Experiments included RT-qPCR, Western blot, and immunohistochemistry on NSCLC patient samples, in vitro studies on isolated CAFs cells, and in vivo nude mouse tumor models.
resultsFifteen key genes associated with radiotherapy resistance in NSCLC cells were identified. SMAD3 was recognized as an independent prognostic factor for NSCLC, linked to poor patient outcomes. High expression of SMAD3 was correlated with low DNA methylation in its promoter region and was enriched in CAFs. In vitro and in vivo experiments confirmed that SMAD3 promotes radiotherapy resistance by activating the ITGA6/PI3K/Akt signaling pathway.
conclusionHigh expression of SMAD3 in NSCLC tissues, cells, and CAFs is closely associated with poor prognosis and increased radiotherapy resistance. SMAD3 is likely to enhance radiotherapy resistance in NSCLC cells by activating the ITGA6/PI3K/Akt signaling pathway.
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