RNF138 contributes to cisplatin resistance in nasopharyngeal carcinoma cells
Abstract Resistance to chemotherapy is a significant concern in the treatment of nasopharyngeal carcinoma (NPC), and occurs due to various mechanisms. This study is aimed to evaluate the effects of RING finger protein 138 (RNF138) in the development of cisplatin resistance to NPC. After gene overexp...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-85716-6 |
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| author | Hangyu Xu Qing Yin Linna Fan Yating Zhao Biying Song Qifan Xu Jie Zhu Meifen Xu |
| author_facet | Hangyu Xu Qing Yin Linna Fan Yating Zhao Biying Song Qifan Xu Jie Zhu Meifen Xu |
| author_sort | Hangyu Xu |
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| description | Abstract Resistance to chemotherapy is a significant concern in the treatment of nasopharyngeal carcinoma (NPC), and occurs due to various mechanisms. This study is aimed to evaluate the effects of RING finger protein 138 (RNF138) in the development of cisplatin resistance to NPC. After gene overexpression and silencing, the expression levels of RNF138 were evaluated. The impacts of RNF138 on the proliferation and apoptosis rate of NPC cells were then assessed. γ-H2AX-mediated DNA damage was determined via immunofluorescence assay. Moreover, a tumor xenograft mouse model was developed to investigate the role of RNF138 on NPC progression in vivo. Additionally, transcriptome analysis was performed in 5–8 F cells transfection with OE-RNF1138 or OE-NC.Cisplatin significantly inhibited the proliferation, and promoted apoptosis and DNA damage in NPC cells; however, overexpression of RNF138 reversed the aforementioned regulatory role of cisplatin on NPC cells. Knockdown of RNF138 resulted in contrasting phenotypic outcomes. Additionally, in nude mice, RNF138 overexpression attenuated the suppressive effects of cisplatin on the growth of xenograft tumor, while RNF138 silencing further enhanced the inhibiting role of cisplatin. We further indicated that in 5–8 F cells following RNF138 overexpression, some pathways such as PI3K-Akt signaling pathway, human papillomavirus infection and ErbB signaling pathway that have been reported to be associated with NPC progression and cisplatin resistance were significantly enriched. These findings indicate that the modulation of RNF138 could potentially address the issue of chemotherapy failure by overcoming cisplatin resistance in NPC cells, making it a promising candidate for targeted drug therapy. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-3fc28939dfae49a8b463673bb54b4db92025-01-12T12:23:38ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-85716-6RNF138 contributes to cisplatin resistance in nasopharyngeal carcinoma cellsHangyu Xu0Qing Yin1Linna Fan2Yating Zhao3Biying Song4Qifan Xu5Jie Zhu6Meifen Xu7Department of Otolaryngology, Taizhou Central Hospital (Taizhou University Hospital)Department of Otolaryngology, Taizhou Central Hospital (Taizhou University Hospital)School of Laboratory Medicine and Life Sciences, Wenzhou Medical UniversityDepartment of Clinical Laboratory, Taizhou Central Hospital (Taizhou University Hospital)Department of Clinical Laboratory, Taizhou Central Hospital (Taizhou University Hospital)Department of Clinical Laboratory, Taizhou Central Hospital (Taizhou University Hospital)Department of Clinical Laboratory, Taizhou Central Hospital (Taizhou University Hospital)Department of Clinical Laboratory, Taizhou Central Hospital (Taizhou University Hospital)Abstract Resistance to chemotherapy is a significant concern in the treatment of nasopharyngeal carcinoma (NPC), and occurs due to various mechanisms. This study is aimed to evaluate the effects of RING finger protein 138 (RNF138) in the development of cisplatin resistance to NPC. After gene overexpression and silencing, the expression levels of RNF138 were evaluated. The impacts of RNF138 on the proliferation and apoptosis rate of NPC cells were then assessed. γ-H2AX-mediated DNA damage was determined via immunofluorescence assay. Moreover, a tumor xenograft mouse model was developed to investigate the role of RNF138 on NPC progression in vivo. Additionally, transcriptome analysis was performed in 5–8 F cells transfection with OE-RNF1138 or OE-NC.Cisplatin significantly inhibited the proliferation, and promoted apoptosis and DNA damage in NPC cells; however, overexpression of RNF138 reversed the aforementioned regulatory role of cisplatin on NPC cells. Knockdown of RNF138 resulted in contrasting phenotypic outcomes. Additionally, in nude mice, RNF138 overexpression attenuated the suppressive effects of cisplatin on the growth of xenograft tumor, while RNF138 silencing further enhanced the inhibiting role of cisplatin. We further indicated that in 5–8 F cells following RNF138 overexpression, some pathways such as PI3K-Akt signaling pathway, human papillomavirus infection and ErbB signaling pathway that have been reported to be associated with NPC progression and cisplatin resistance were significantly enriched. These findings indicate that the modulation of RNF138 could potentially address the issue of chemotherapy failure by overcoming cisplatin resistance in NPC cells, making it a promising candidate for targeted drug therapy.https://doi.org/10.1038/s41598-025-85716-6Nasopharyngeal carcinomaRNF138Cisplatin resistanceProliferationApoptosisDNA damage |
| spellingShingle | Hangyu Xu Qing Yin Linna Fan Yating Zhao Biying Song Qifan Xu Jie Zhu Meifen Xu RNF138 contributes to cisplatin resistance in nasopharyngeal carcinoma cells Scientific Reports Nasopharyngeal carcinoma RNF138 Cisplatin resistance Proliferation Apoptosis DNA damage |
| title | RNF138 contributes to cisplatin resistance in nasopharyngeal carcinoma cells |
| title_full | RNF138 contributes to cisplatin resistance in nasopharyngeal carcinoma cells |
| title_fullStr | RNF138 contributes to cisplatin resistance in nasopharyngeal carcinoma cells |
| title_full_unstemmed | RNF138 contributes to cisplatin resistance in nasopharyngeal carcinoma cells |
| title_short | RNF138 contributes to cisplatin resistance in nasopharyngeal carcinoma cells |
| title_sort | rnf138 contributes to cisplatin resistance in nasopharyngeal carcinoma cells |
| topic | Nasopharyngeal carcinoma RNF138 Cisplatin resistance Proliferation Apoptosis DNA damage |
| url | https://doi.org/10.1038/s41598-025-85716-6 |
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