ArticleScientific reports2024
The immune regulation and therapeutic potential of the SMAD gene family in breast cancer.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 7 citations in OpenAlex.
- Immunological and prognostic impact of NRF2 in high grade serous ovarian cancer.Genes and immunity · 2026Article
- BART-spatial unravels biologically significant transcriptional regulators from spatial omics data.bioRxiv : the preprint server for biology · 2026Article
- miR-3648 regulates cell functions and acts as a potential biomarker to predict prognosis in breast cancer and its bioinformatics analysis.World journal of surgical oncology · 2026Article
- Clinical impact of the methylation status of SMAD4 and AKR1B1 genes in a liquid biopsy sample as a prognostic marker for breast cancer.Scientific reports · 2026Article
- [Expression and prognostic value of mothers against decapentaplegic homolog 7 in head and neck squamous cell carcinoma].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2025Article
- The Role of RAC2 and PTTG1 in Cancer Biology.Cells · 2025Review
- Suppression of chemically induced mammary cancer by early-life oral administration of cholera toxin in mice is associated with aberrant regulation of Bmp and Notch signaling pathways.Molecular biology reports · 2025Article
- miRNA-driven sensitization of breast cancer cells to Doxorubicin treatment following exposure to low dose of Zinc Oxide nanoparticles.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- miRNAs in Signal Transduction of SMAD Proteins in Breast Cancer.International journal of molecular sciences · 2024Article
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Authors and funding
7 authors at 2 institutions in 1 country.
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Abstract
Breast cancer is a serious threat to human health. The transforming growth factor-β signaling pathway is an important pathway involved in the occurrence and development of cancer. The SMAD family genes are responsible for the TGF-β signaling pathway. However, the mechanism by which genes of the SMAD family are involved in breast cancer is still unclear. Therefore, it is necessary to investigate the biological roles of the SMAD family genes in breast cancer. We downloaded the gene expression data, gene mutation data, and clinical pathological data of breast cancer patients from the UCSC Xena database. We used the Wilcox test to estimate the expression of genes of the SMAD family in cancers. And the biological functions of SMAD family genes using the DAVID website. The Pearson correlation method was used to explore the immune cell infiltration and drug response of SMAD family genes. We conducted in biological experiments vitro and vivo. In this study, we integrated the multi-omics data from TCGA breast cancer patients for analysis. The expression of genes of SMAD family was significantly dysregulated in patients with breast cancer. Except for SMAD6, the expression of other SMAD family genes was positively correlated. We also found that genes of the SMAD family were significantly enriched in the TGF-β signaling pathway, Hippo signaling pathway, cell cycle, and cancer-related pathways. In addition, SMAD3, SMAD6, and SMAD7 were lowly expressed in stage II breast cancer, while SMAD4 and SMAD2 were lowly expressed in stage III cancer. Furthermore, the expression of genes of the SMAD family was significantly correlated with immune cell infiltration scores. Constructing a xenograft tumor mouse model, we found that SMAD3 knockdown significantly inhibited tumorigenesis. Finally, we analyzed the association between these genes and the IC50 value of drugs. Interestingly, patients with high expression of SMAD3 exhibited significant resistance to dasatinib and staurosporine, while high sensitivity to tamoxifen and auranofin. In addition, SMAD3 knockdown promoted the apoptosis of BT-549 cells and decreased cell activity, and BAY-1161909 and XK-469 increased drug efficacy. In conclusion, genes of the SMAD family play a crucial role in the development of breast cancer.
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