IGF2BP3 As a Prognostic Biomarker and Regulator of Metastasis in Merkel Cell Carcinoma
Merkel cell carcinoma (MCC) is an aggressive skin cancer with frequent metastasis; however, effective treatment options for advanced disease are often lacking. In this study, we investigated the clinical significance and functional impact of IGF2 mRNA-binding protein 3 (IGF2BP3) in MCC. Our results...
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Elsevier
2025-05-01
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| Series: | JID Innovations |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667026725000098 |
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| author | Yajie Yang Jiwei Gao Hao Shi Harri Sihto Sami Kilpinen François Vilcot Libuse Janská Jakob Jeschonneck Todor Cvetanovic Anders Höög Jan Siarov John Paoli C. Christofer Juhlin Lisa Villabona Catharina Larsson Weng-Onn Lui |
| author_facet | Yajie Yang Jiwei Gao Hao Shi Harri Sihto Sami Kilpinen François Vilcot Libuse Janská Jakob Jeschonneck Todor Cvetanovic Anders Höög Jan Siarov John Paoli C. Christofer Juhlin Lisa Villabona Catharina Larsson Weng-Onn Lui |
| author_sort | Yajie Yang |
| collection | DOAJ |
| description | Merkel cell carcinoma (MCC) is an aggressive skin cancer with frequent metastasis; however, effective treatment options for advanced disease are often lacking. In this study, we investigated the clinical significance and functional impact of IGF2 mRNA-binding protein 3 (IGF2BP3) in MCC. Our results revealed elevated IGF2BP3 expression in metastases compared to that in primary tumors. High IGF2BP3 levels in primary MCCs were associated with shorter disease-specific survival rates. In an MCC xenograft model, the lung metastases exhibited increased IGF2BP3 expression. Functional studies showed that IGF2BP3 primarily regulates MCC cell migration and invasion. We identified 281 direct RNA targets of IGF2BP3 with enriched functions linked to metastasis-related processes, and several targets overlapped with genes differentially expressed between MCC primary tumors and metastases, implying that IGF2BP3 and its targets contribute to tumor progression. Inhibition or silencing of bromodomain-containing protein 4 reduced IGF2BP3 expression, suggesting that bromodomain-containing protein 4 is a potential regulator of IGF2BP3. Our study underscores the role of IGF2BP3 in MCC metastasis and its potential as a prognostic biomarker. |
| format | Article |
| id | doaj-art-1c110571b91d41f580addfd67dc85645 |
| institution | DOAJ |
| issn | 2667-0267 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JID Innovations |
| spelling | doaj-art-1c110571b91d41f580addfd67dc856452025-08-20T03:10:27ZengElsevierJID Innovations2667-02672025-05-015310035510.1016/j.xjidi.2025.100355IGF2BP3 As a Prognostic Biomarker and Regulator of Metastasis in Merkel Cell CarcinomaYajie Yang0Jiwei Gao1Hao Shi2Harri Sihto3Sami Kilpinen4François Vilcot5Libuse Janská6Jakob Jeschonneck7Todor Cvetanovic8Anders Höög9Jan Siarov10John Paoli11C. Christofer Juhlin12Lisa Villabona13Catharina Larsson14Weng-Onn Lui15Department of Oncology-Pathology, Karolinska Institutet and BioClinicum, Karolinska University Hospital, Solna, Sweden; Correspondence: Yajie Yang, BioClinicum J6:20, Karolinska University Hospital, SE-171 64 Solna, Sweden.Department of Oncology-Pathology, Karolinska Institutet and BioClinicum, Karolinska University Hospital, Solna, SwedenDepartment of Oncology-Pathology, Karolinska Institutet and BioClinicum, Karolinska University Hospital, Solna, SwedenDepartment of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandMolecular and Integrative Biosciences Research Programme, University of Helsinki, Helsinki, FinlandDepartment of Oncology-Pathology, Karolinska Institutet and BioClinicum, Karolinska University Hospital, Solna, SwedenDepartment of Oncology-Pathology, Karolinska Institutet and BioClinicum, Karolinska University Hospital, Solna, SwedenDepartment of Oncology-Pathology, Karolinska Institutet and BioClinicum, Karolinska University Hospital, Solna, SwedenDepartment of Oncology-Pathology, Karolinska Institutet and BioClinicum, Karolinska University Hospital, Solna, SwedenDepartment of Oncology-Pathology, Karolinska Institutet and BioClinicum, Karolinska University Hospital, Solna, Sweden; Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Dermatology and Venereology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Oncology-Pathology, Karolinska Institutet and BioClinicum, Karolinska University Hospital, Solna, Sweden; Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of Oncology-Pathology, Karolinska Institutet and BioClinicum, Karolinska University Hospital, Solna, SwedenDepartment of Oncology-Pathology, Karolinska Institutet and BioClinicum, Karolinska University Hospital, Solna, Sweden; Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of Oncology-Pathology, Karolinska Institutet and BioClinicum, Karolinska University Hospital, Solna, Sweden; Weng-Onn Lui, BioClinicum J6:20, Karolinska University Hospital, SE-171 64 Solna, Sweden.Merkel cell carcinoma (MCC) is an aggressive skin cancer with frequent metastasis; however, effective treatment options for advanced disease are often lacking. In this study, we investigated the clinical significance and functional impact of IGF2 mRNA-binding protein 3 (IGF2BP3) in MCC. Our results revealed elevated IGF2BP3 expression in metastases compared to that in primary tumors. High IGF2BP3 levels in primary MCCs were associated with shorter disease-specific survival rates. In an MCC xenograft model, the lung metastases exhibited increased IGF2BP3 expression. Functional studies showed that IGF2BP3 primarily regulates MCC cell migration and invasion. We identified 281 direct RNA targets of IGF2BP3 with enriched functions linked to metastasis-related processes, and several targets overlapped with genes differentially expressed between MCC primary tumors and metastases, implying that IGF2BP3 and its targets contribute to tumor progression. Inhibition or silencing of bromodomain-containing protein 4 reduced IGF2BP3 expression, suggesting that bromodomain-containing protein 4 is a potential regulator of IGF2BP3. Our study underscores the role of IGF2BP3 in MCC metastasis and its potential as a prognostic biomarker.http://www.sciencedirect.com/science/article/pii/S2667026725000098BiomarkerIGF2BP3Merkel cell carcinomaMetastasis |
| spellingShingle | Yajie Yang Jiwei Gao Hao Shi Harri Sihto Sami Kilpinen François Vilcot Libuse Janská Jakob Jeschonneck Todor Cvetanovic Anders Höög Jan Siarov John Paoli C. Christofer Juhlin Lisa Villabona Catharina Larsson Weng-Onn Lui IGF2BP3 As a Prognostic Biomarker and Regulator of Metastasis in Merkel Cell Carcinoma JID Innovations Biomarker IGF2BP3 Merkel cell carcinoma Metastasis |
| title | IGF2BP3 As a Prognostic Biomarker and Regulator of Metastasis in Merkel Cell Carcinoma |
| title_full | IGF2BP3 As a Prognostic Biomarker and Regulator of Metastasis in Merkel Cell Carcinoma |
| title_fullStr | IGF2BP3 As a Prognostic Biomarker and Regulator of Metastasis in Merkel Cell Carcinoma |
| title_full_unstemmed | IGF2BP3 As a Prognostic Biomarker and Regulator of Metastasis in Merkel Cell Carcinoma |
| title_short | IGF2BP3 As a Prognostic Biomarker and Regulator of Metastasis in Merkel Cell Carcinoma |
| title_sort | igf2bp3 as a prognostic biomarker and regulator of metastasis in merkel cell carcinoma |
| topic | Biomarker IGF2BP3 Merkel cell carcinoma Metastasis |
| url | http://www.sciencedirect.com/science/article/pii/S2667026725000098 |
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