دورية أكاديمية
Inhibition of non-small cell lung cancer metastasis by knocking down APE1 through regulating myeloid-derived suppressor cells-induced immune disorders.
| العنوان: | Inhibition of non-small cell lung cancer metastasis by knocking down APE1 through regulating myeloid-derived suppressor cells-induced immune disorders. |
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| المؤلفون: | Zhang Z; The Affiliated Hospital, Fujian Medical University, Fuzhou 362002, China.; The Shengli Clinical Medical College, Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, China., Lin Y; The Shengli Clinical Medical College, Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, China., Pan X; The Shengli Clinical Medical College, Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, China., Chen S; The Affiliated Hospital, Fujian Medical University, Fuzhou 362002, China. |
| المصدر: | Aging [Aging (Albany NY)] 2024 Jun 14; Vol. 16 (12), pp. 10435-10445. Date of Electronic Publication: 2024 Jun 14. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Impact Journals, LLC Country of Publication: United States NLM ID: 101508617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1945-4589 (Electronic) Linking ISSN: 19454589 NLM ISO Abbreviation: Aging (Albany NY) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Albany, NY : Impact Journals, LLC |
| مواضيع طبية MeSH: | Myeloid-Derived Suppressor Cells*/immunology , Myeloid-Derived Suppressor Cells*/metabolism , Carcinoma, Non-Small-Cell Lung*/genetics , Carcinoma, Non-Small-Cell Lung*/pathology , Carcinoma, Non-Small-Cell Lung*/immunology , Carcinoma, Non-Small-Cell Lung*/metabolism , Lung Neoplasms*/genetics , Lung Neoplasms*/immunology , Lung Neoplasms*/pathology , Lung Neoplasms*/secondary , Lung Neoplasms*/metabolism , DNA-(Apurinic or Apyrimidinic Site) Lyase*/genetics , DNA-(Apurinic or Apyrimidinic Site) Lyase*/metabolism , Granulocyte-Macrophage Colony-Stimulating Factor*/metabolism , Granulocyte-Macrophage Colony-Stimulating Factor*/genetics, Animals ; Humans ; Mice ; A549 Cells ; Gene Knockdown Techniques ; Neoplasm Metastasis ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Male ; Female |
| مستخلص: | Background: Non-small cell lung cancer (NSCLC) represents a highly immunogenic malignancy. Immunologic tolerance facilitated by myeloid-derived suppressor cells (MDSCs) is implicated in primary or secondary resistance mechanisms in NSCLC. The potential role of APE1 in regulating NSCLC metastasis by targeting MDSCs remains uncertain. Methods: This study utilized a plasmid, Plxpsp-mGM-CSF, to induce elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in A549 cells. Tumor transplantation experiments involved A549, A549+GM-CSF, and A549+GM-CSF-siAPE1 cell lines. Evaluation encompassed MDSCs, Treg cells, IgG, CD3, and CD8 levels. Results: Notably, lung cancer tissues and cells displayed markedly reduced APE1 expression. siAPE1 transfection significantly curtailed tumor growth compared to the A549+GM-CSF group. APE1 knockdown orchestrated immune system modulation in lung tumor mice, characterized by diminished MDSCs but augmented Treg cells, IgG, CD3, and CD8. Additionally, APE1 knockdown led to reduced levels of pro-MDSC cytokines (HGF, CCL5, IL-6, CCL12) and a concurrent upregulation of the anti-MDSC cytokine IL-1ra. Furthermore, APE1 knockdown impeded cell viability in both A549 and H1650 cells. Conclusions: Transplantation of A549-GM-CSF amplified MDSC levels, fostering accelerated tumor growth, while mitigating MDSC levels through APE1 knockdown hindered tumor progression and alleviated inflammatory infiltration in lung cancer tissues. Strategies targeting the APE1/MDSC axis offer a promising approach for lung cancer prevention and treatment, presenting novel insights for NSCLC management. |
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| فهرسة مساهمة: | Keywords: A549; APE1; MDSCs; NSCLC; tumor immune |
| المشرفين على المادة: | EC 4.2.99.18 (DNA-(Apurinic or Apyrimidinic Site) Lyase) 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) |
| تواريخ الأحداث: | Date Created: 20240617 Date Completed: 20240705 Latest Revision: 20240730 |
| رمز التحديث: | 20240730 |
| مُعرف محوري في PubMed: | PMC11236315 |
| DOI: | 10.18632/aging.205938 |
| PMID: | 38885059 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1945-4589 |
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| DOI: | 10.18632/aging.205938 |