miR-1246 enhances chemo-resistance of polyploid giant cancer cells in H1299 cells by targeting GSK3β/β-catenin
Abstract Non-small cell lung cancer (NSCLC) is characterized by a high mortality rate. Chemotherapy has been observed to potentially increase the prevalence of polyploid giant cancer cells (PGCCs), which may play a role in the development of chemo-resistance in NSCLC. The dysregulated expression of...
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| Format: | Article |
| Language: | English |
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Springer
2025-05-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02756-0 |
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| author | Lili Wang Zien Yang Sining Xing Song Zhao Mingyue Ouyang Huiying Yu |
| author_facet | Lili Wang Zien Yang Sining Xing Song Zhao Mingyue Ouyang Huiying Yu |
| author_sort | Lili Wang |
| collection | DOAJ |
| description | Abstract Non-small cell lung cancer (NSCLC) is characterized by a high mortality rate. Chemotherapy has been observed to potentially increase the prevalence of polyploid giant cancer cells (PGCCs), which may play a role in the development of chemo-resistance in NSCLC. The dysregulated expression of miR-1246 has been implicated in the modulation of gene expression related to drug resistance. Therefore, the objective of this study is to examine the role of miRNA-1246 in PGCCs and to elucidate its regulatory mechanisms. H1299 cells were treated with 100 nM docetaxel (Doc) for 24 h, then allowed to recover for 3 days to form polyploid giant cancer cells (PGCCs). The miRNA profiles of these PGCCs were analyzed, focusing on miR-1246. Transfection with miR-1246 mimics or inhibitors was performed, and various assays were used to assess the effects of miR-1246 inn PGCCs. The study found miR-1246 levels were significantly higher in PGCCs than in the original cells, affecting chemo-resistance, apoptosis, migration, and epithelial-mesenchymal transition. These findings suggested that NSCLC H1299 cells may employ polyploidy formation as a survival mechanism in response to docetaxel-based treatment, mediated by the miR-1246/GSK3β/β-catenin axis, ultimately leading to enhanced chemo-resistance. |
| format | Article |
| id | doaj-art-ea45e6f4d62f40fd9f378d58bf6e302a |
| institution | DOAJ |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-ea45e6f4d62f40fd9f378d58bf6e302a2025-08-20T03:08:25ZengSpringerDiscover Oncology2730-60112025-05-0116111310.1007/s12672-025-02756-0miR-1246 enhances chemo-resistance of polyploid giant cancer cells in H1299 cells by targeting GSK3β/β-cateninLili Wang0Zien Yang1Sining Xing2Song Zhao3Mingyue Ouyang4Huiying Yu5Laboratory of Basic Medicine, General Hospital of Northern Theatre CommandLaboratory of Basic Medicine, General Hospital of Northern Theatre CommandLaboratory of Basic Medicine, General Hospital of Northern Theatre CommandLaboratory of Basic Medicine, General Hospital of Northern Theatre CommandLaboratory of Basic Medicine, General Hospital of Northern Theatre CommandLaboratory of Basic Medicine, General Hospital of Northern Theatre CommandAbstract Non-small cell lung cancer (NSCLC) is characterized by a high mortality rate. Chemotherapy has been observed to potentially increase the prevalence of polyploid giant cancer cells (PGCCs), which may play a role in the development of chemo-resistance in NSCLC. The dysregulated expression of miR-1246 has been implicated in the modulation of gene expression related to drug resistance. Therefore, the objective of this study is to examine the role of miRNA-1246 in PGCCs and to elucidate its regulatory mechanisms. H1299 cells were treated with 100 nM docetaxel (Doc) for 24 h, then allowed to recover for 3 days to form polyploid giant cancer cells (PGCCs). The miRNA profiles of these PGCCs were analyzed, focusing on miR-1246. Transfection with miR-1246 mimics or inhibitors was performed, and various assays were used to assess the effects of miR-1246 inn PGCCs. The study found miR-1246 levels were significantly higher in PGCCs than in the original cells, affecting chemo-resistance, apoptosis, migration, and epithelial-mesenchymal transition. These findings suggested that NSCLC H1299 cells may employ polyploidy formation as a survival mechanism in response to docetaxel-based treatment, mediated by the miR-1246/GSK3β/β-catenin axis, ultimately leading to enhanced chemo-resistance.https://doi.org/10.1007/s12672-025-02756-0Non-small cell lung cancerPolyploid giant cancer cellsmiR-1246GSK3ββ-cateninChemo-resistance |
| spellingShingle | Lili Wang Zien Yang Sining Xing Song Zhao Mingyue Ouyang Huiying Yu miR-1246 enhances chemo-resistance of polyploid giant cancer cells in H1299 cells by targeting GSK3β/β-catenin Discover Oncology Non-small cell lung cancer Polyploid giant cancer cells miR-1246 GSK3β β-catenin Chemo-resistance |
| title | miR-1246 enhances chemo-resistance of polyploid giant cancer cells in H1299 cells by targeting GSK3β/β-catenin |
| title_full | miR-1246 enhances chemo-resistance of polyploid giant cancer cells in H1299 cells by targeting GSK3β/β-catenin |
| title_fullStr | miR-1246 enhances chemo-resistance of polyploid giant cancer cells in H1299 cells by targeting GSK3β/β-catenin |
| title_full_unstemmed | miR-1246 enhances chemo-resistance of polyploid giant cancer cells in H1299 cells by targeting GSK3β/β-catenin |
| title_short | miR-1246 enhances chemo-resistance of polyploid giant cancer cells in H1299 cells by targeting GSK3β/β-catenin |
| title_sort | mir 1246 enhances chemo resistance of polyploid giant cancer cells in h1299 cells by targeting gsk3β β catenin |
| topic | Non-small cell lung cancer Polyploid giant cancer cells miR-1246 GSK3β β-catenin Chemo-resistance |
| url | https://doi.org/10.1007/s12672-025-02756-0 |
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