CSNK1E is involved in TGF-β1 induced epithelial mesenchymal transformationas and related to melanoma immune heterogeneity
IntroductionMelanoma (MM), the deadliest form of skin cancer, originates from melanocytes. Despite advances in immunotherapy that have somewhat improved the prognosis for MM patients, high levels of resistance to treatment continue to result in poor clinical outcomes. Identifying novel biomarkers an...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1501849/full |
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| author | Wangbing Hong Xin Wang Xinyu Huang Pengfei Chen Yifan Liu Ziying Zheng Xin You Yinghua Chen Zengxin Xie Gongnan Zhan Heping Huang |
| author_facet | Wangbing Hong Xin Wang Xinyu Huang Pengfei Chen Yifan Liu Ziying Zheng Xin You Yinghua Chen Zengxin Xie Gongnan Zhan Heping Huang |
| author_sort | Wangbing Hong |
| collection | DOAJ |
| description | IntroductionMelanoma (MM), the deadliest form of skin cancer, originates from melanocytes. Despite advances in immunotherapy that have somewhat improved the prognosis for MM patients, high levels of resistance to treatment continue to result in poor clinical outcomes. Identifying novel biomarkers and therapeutic targets is critical for improving the prognosis and treatment of MM.MethodsIn this study, we analyzed the expression patterns of WNT signaling pathway genes in MM and explored their potential mechanisms. Using Cox regression analysis, we identified 19 prognostic-related genes. Consistency clustering was performed to evaluate the potential of these genes as classifiers for prognosis. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was then applied to refine the gene set and construct a 13-gene prognostic model. We validated the model at multiple time points to assess its predictive performance. Additionally, correlation analyses were performed to investigate the relationships between key genes and processes, including epithelial-to-mesenchymal transition (EMT) and immune responses.ResultsWe identified that CSNK1E and RAC3 were significantly positively correlated with the EMT process, with CSNK1E showing a similar expression trend to EMT-related genes. Both genes were also negatively correlated with multiple immune cell types and immune checkpoint genes. The 13-gene prognostic model demonstrated excellent predictive performance in MM prognosis. Pan-cancer analysis further revealed heterogeneous expression patterns and prognostic potential of CSNK1E across various cancers. Wet experiments confirmed that CSNK1E promotes MM cell proliferation, invasion, and migration, and enhances malignant progression through the TGF-β signaling pathway.DiscussionOur findings suggest that CSNK1E plays a crucial role in MM progression and could serve as a potential therapeutic target. The WNT and TGF-β pathways may work synergistically in regulating the EMT process in MM, highlighting their potential as novel therapeutic targets. These insights may contribute to the development of more effective treatments for MM, particularly for overcoming resistance to current therapies. |
| format | Article |
| id | doaj-art-9a56b5ca57b14345af47a8295afbda0c |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-9a56b5ca57b14345af47a8295afbda0c2025-01-13T16:44:07ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15018491501849CSNK1E is involved in TGF-β1 induced epithelial mesenchymal transformationas and related to melanoma immune heterogeneityWangbing Hong0Xin Wang1Xinyu Huang2Pengfei Chen3Yifan Liu4Ziying Zheng5Xin You6Yinghua Chen7Zengxin Xie8Gongnan Zhan9Heping Huang10Department of Plastic and Cosmetic Surgery, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaMedical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Plastic and Cosmetic Surgery, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaDepartment of Plastic and Cosmetic Surgery, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaDepartment of Plastic and Cosmetic Surgery, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaDepartment of Plastic and Cosmetic Surgery, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaDepartment of Plastic and Cosmetic Surgery, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaDepartment of Plastic and Cosmetic Surgery, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaDepartment of Plastic and Cosmetic Surgery, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaDepartment of Plastic and Cosmetic Surgery, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaIntroductionMelanoma (MM), the deadliest form of skin cancer, originates from melanocytes. Despite advances in immunotherapy that have somewhat improved the prognosis for MM patients, high levels of resistance to treatment continue to result in poor clinical outcomes. Identifying novel biomarkers and therapeutic targets is critical for improving the prognosis and treatment of MM.MethodsIn this study, we analyzed the expression patterns of WNT signaling pathway genes in MM and explored their potential mechanisms. Using Cox regression analysis, we identified 19 prognostic-related genes. Consistency clustering was performed to evaluate the potential of these genes as classifiers for prognosis. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was then applied to refine the gene set and construct a 13-gene prognostic model. We validated the model at multiple time points to assess its predictive performance. Additionally, correlation analyses were performed to investigate the relationships between key genes and processes, including epithelial-to-mesenchymal transition (EMT) and immune responses.ResultsWe identified that CSNK1E and RAC3 were significantly positively correlated with the EMT process, with CSNK1E showing a similar expression trend to EMT-related genes. Both genes were also negatively correlated with multiple immune cell types and immune checkpoint genes. The 13-gene prognostic model demonstrated excellent predictive performance in MM prognosis. Pan-cancer analysis further revealed heterogeneous expression patterns and prognostic potential of CSNK1E across various cancers. Wet experiments confirmed that CSNK1E promotes MM cell proliferation, invasion, and migration, and enhances malignant progression through the TGF-β signaling pathway.DiscussionOur findings suggest that CSNK1E plays a crucial role in MM progression and could serve as a potential therapeutic target. The WNT and TGF-β pathways may work synergistically in regulating the EMT process in MM, highlighting their potential as novel therapeutic targets. These insights may contribute to the development of more effective treatments for MM, particularly for overcoming resistance to current therapies.https://www.frontiersin.org/articles/10.3389/fphar.2024.1501849/fullCSNK1ETGF-β 1epithelial mesenchymal transformationamelanomaLASSO |
| spellingShingle | Wangbing Hong Xin Wang Xinyu Huang Pengfei Chen Yifan Liu Ziying Zheng Xin You Yinghua Chen Zengxin Xie Gongnan Zhan Heping Huang CSNK1E is involved in TGF-β1 induced epithelial mesenchymal transformationas and related to melanoma immune heterogeneity Frontiers in Pharmacology CSNK1E TGF-β 1 epithelial mesenchymal transformationa melanoma LASSO |
| title | CSNK1E is involved in TGF-β1 induced epithelial mesenchymal transformationas and related to melanoma immune heterogeneity |
| title_full | CSNK1E is involved in TGF-β1 induced epithelial mesenchymal transformationas and related to melanoma immune heterogeneity |
| title_fullStr | CSNK1E is involved in TGF-β1 induced epithelial mesenchymal transformationas and related to melanoma immune heterogeneity |
| title_full_unstemmed | CSNK1E is involved in TGF-β1 induced epithelial mesenchymal transformationas and related to melanoma immune heterogeneity |
| title_short | CSNK1E is involved in TGF-β1 induced epithelial mesenchymal transformationas and related to melanoma immune heterogeneity |
| title_sort | csnk1e is involved in tgf β1 induced epithelial mesenchymal transformationas and related to melanoma immune heterogeneity |
| topic | CSNK1E TGF-β 1 epithelial mesenchymal transformationa melanoma LASSO |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1501849/full |
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