Intervening Non-Small-Cell Lung Cancer Progression by Cell Membrane Coated Platycodin D via Regulating Hsa-miR-1246/FUT9/GSK3β Pathway
Shuyu Zheng,1,2 Zejuan Xie,1 Ziao Zhou,1 Shanshan Wang,1 Yanlin Xin,1 Jiamin Lin,1 Keyu Cheng,1 Tianming Lu,1 Ruogu Qi,1 Yuanyuan Guo1 1Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, P...
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Dove Medical Press
2025-02-01
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| author | Zheng S Xie Z Zhou Z Wang S Xin Y Lin J Cheng K Lu T Qi R Guo Y |
| author_facet | Zheng S Xie Z Zhou Z Wang S Xin Y Lin J Cheng K Lu T Qi R Guo Y |
| author_sort | Zheng S |
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| description | Shuyu Zheng,1,2 Zejuan Xie,1 Ziao Zhou,1 Shanshan Wang,1 Yanlin Xin,1 Jiamin Lin,1 Keyu Cheng,1 Tianming Lu,1 Ruogu Qi,1 Yuanyuan Guo1 1Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang Province, 310009, People’s Republic of ChinaCorrespondence: Ruogu Qi; Yuanyuan Guo, Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Email [email protected]; [email protected]: Metastatic non-small cell lung cancer (NSCLC) remains a global health threat, with patients facing inevitable disease progression despite standard-of-care therapy. Prior studies showed Platycodin D (PD)-induced cell cycle arrest and apoptosis in NSCLC via RNA regulatory network, yet elucidating PD’s mechanisms in NSCLC progression is challenging in the real world.Methods: Biological effects of PD on NSCLC cell lines A549 and PC-9 were assessed through in vitro assays, encompassing apoptosis, proliferation, colony formation, migration and invasion. MicroRNAs (miRNAs) expression was profiled, and their roles were investigated using miRNA mimics or inhibitors. Predicted miRNA targets were validated via dual-luciferase reporter assays and Western blotting following bioinformatic prediction. PD’s metastatic inhibitory potential in NSCLC was evaluated in an in vivo lung cancer metastasis model. Furthermore, a homologous cell membrane-based PD delivery system was established to improve the biosafety and efficacy of PD in vivo.Results: Hsa-miR-1246 was upregulated by PD treatment, and functional experiments demonstrated that the miR-1246-mimic enhanced PD’s suppressive effects on NSCLC cell proliferation, colony formation, migration, and invasion, while the miR-1246-inhibitor abrogated these effects. Notably, dual-luciferase assays confirmed that hsa-miR-1246 directly targeted the 3’ untranslated regions (3’ UTRs) of Fucosyltransferase 9 (FUT9), modulating its expression. Moreover, the hsa-miR-1246/FUT9 axis regulated the phosphorylation level and expression of GSK3β protein. In vivo, PD encapsulated in homologous cell membranes mitigated tumor growth and migration in metastatic NSCLC mice with minimal side effects.Conclusion: The application of PD prompted an increase in the expression levels of hsa-miR-1246 and a concurrent decrease in FUT9. Importantly, the therapeutic efficacy of PD in vivo was markedly enhanced through homologous cell delivery system. Collectively, this study revealed the potential utility of PD in the treatment of NSCLC progression.Keywords: non-small cell lung cancer, platycodin D, anti-cancer phytomedicine, hsa-miR-1246, FUT9, cancer cell membrane |
| format | Article |
| id | doaj-art-88a00ca1387e4fffbcc1e03fd3d2039d |
| institution | Kabale University |
| issn | 1178-2013 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Dove Medical Press |
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| series | International Journal of Nanomedicine |
| spelling | doaj-art-88a00ca1387e4fffbcc1e03fd3d2039d2025-02-06T16:40:24ZengDove Medical PressInternational Journal of Nanomedicine1178-20132025-02-01Volume 201661167899937Intervening Non-Small-Cell Lung Cancer Progression by Cell Membrane Coated Platycodin D via Regulating Hsa-miR-1246/FUT9/GSK3β PathwayZheng SXie ZZhou ZWang SXin YLin JCheng KLu TQi RGuo YShuyu Zheng,1,2 Zejuan Xie,1 Ziao Zhou,1 Shanshan Wang,1 Yanlin Xin,1 Jiamin Lin,1 Keyu Cheng,1 Tianming Lu,1 Ruogu Qi,1 Yuanyuan Guo1 1Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang Province, 310009, People’s Republic of ChinaCorrespondence: Ruogu Qi; Yuanyuan Guo, Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Email [email protected]; [email protected]: Metastatic non-small cell lung cancer (NSCLC) remains a global health threat, with patients facing inevitable disease progression despite standard-of-care therapy. Prior studies showed Platycodin D (PD)-induced cell cycle arrest and apoptosis in NSCLC via RNA regulatory network, yet elucidating PD’s mechanisms in NSCLC progression is challenging in the real world.Methods: Biological effects of PD on NSCLC cell lines A549 and PC-9 were assessed through in vitro assays, encompassing apoptosis, proliferation, colony formation, migration and invasion. MicroRNAs (miRNAs) expression was profiled, and their roles were investigated using miRNA mimics or inhibitors. Predicted miRNA targets were validated via dual-luciferase reporter assays and Western blotting following bioinformatic prediction. PD’s metastatic inhibitory potential in NSCLC was evaluated in an in vivo lung cancer metastasis model. Furthermore, a homologous cell membrane-based PD delivery system was established to improve the biosafety and efficacy of PD in vivo.Results: Hsa-miR-1246 was upregulated by PD treatment, and functional experiments demonstrated that the miR-1246-mimic enhanced PD’s suppressive effects on NSCLC cell proliferation, colony formation, migration, and invasion, while the miR-1246-inhibitor abrogated these effects. Notably, dual-luciferase assays confirmed that hsa-miR-1246 directly targeted the 3’ untranslated regions (3’ UTRs) of Fucosyltransferase 9 (FUT9), modulating its expression. Moreover, the hsa-miR-1246/FUT9 axis regulated the phosphorylation level and expression of GSK3β protein. In vivo, PD encapsulated in homologous cell membranes mitigated tumor growth and migration in metastatic NSCLC mice with minimal side effects.Conclusion: The application of PD prompted an increase in the expression levels of hsa-miR-1246 and a concurrent decrease in FUT9. Importantly, the therapeutic efficacy of PD in vivo was markedly enhanced through homologous cell delivery system. Collectively, this study revealed the potential utility of PD in the treatment of NSCLC progression.Keywords: non-small cell lung cancer, platycodin D, anti-cancer phytomedicine, hsa-miR-1246, FUT9, cancer cell membranehttps://www.dovepress.com/intervening-non-small-cell-lung-cancer-progression-by-cell-membrane-co-peer-reviewed-fulltext-article-IJNnon-small cell lung cancerplatycodin danti-cancer phytomedicinehsa-mir-1246fut9cancer cell membrane |
| spellingShingle | Zheng S Xie Z Zhou Z Wang S Xin Y Lin J Cheng K Lu T Qi R Guo Y Intervening Non-Small-Cell Lung Cancer Progression by Cell Membrane Coated Platycodin D via Regulating Hsa-miR-1246/FUT9/GSK3β Pathway International Journal of Nanomedicine non-small cell lung cancer platycodin d anti-cancer phytomedicine hsa-mir-1246 fut9 cancer cell membrane |
| title | Intervening Non-Small-Cell Lung Cancer Progression by Cell Membrane Coated Platycodin D via Regulating Hsa-miR-1246/FUT9/GSK3β Pathway |
| title_full | Intervening Non-Small-Cell Lung Cancer Progression by Cell Membrane Coated Platycodin D via Regulating Hsa-miR-1246/FUT9/GSK3β Pathway |
| title_fullStr | Intervening Non-Small-Cell Lung Cancer Progression by Cell Membrane Coated Platycodin D via Regulating Hsa-miR-1246/FUT9/GSK3β Pathway |
| title_full_unstemmed | Intervening Non-Small-Cell Lung Cancer Progression by Cell Membrane Coated Platycodin D via Regulating Hsa-miR-1246/FUT9/GSK3β Pathway |
| title_short | Intervening Non-Small-Cell Lung Cancer Progression by Cell Membrane Coated Platycodin D via Regulating Hsa-miR-1246/FUT9/GSK3β Pathway |
| title_sort | intervening non small cell lung cancer progression by cell membrane coated platycodin d via regulating hsa mir 1246 fut9 gsk3 beta pathway |
| topic | non-small cell lung cancer platycodin d anti-cancer phytomedicine hsa-mir-1246 fut9 cancer cell membrane |
| url | https://www.dovepress.com/intervening-non-small-cell-lung-cancer-progression-by-cell-membrane-co-peer-reviewed-fulltext-article-IJN |
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