NSD3, a member of nuclear receptor‐binding SET domain family, is a potential prognostic biomarker for pancreatic cancer
Abstract Background Members of the nuclear receptor‐binding SET domain (NSD) family of histone H3 lysine 36 methyltransferases comprise NSD1, NSD2 (MMSET/WHSC1), and NSD3 (Wolf–Hirschhorn syndrome candidate 1‐like 1, WHSC1L1). While the expression of NSD genes is essential to normal biological proce...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-05-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.5774 |
| _version_ | 1797817655666671616 |
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| author | Qunli Xiong Ying Zhou Su Zhang Yaguang Zhang Yongfeng Xu Yang Yang Congya Zhou Zhu Zeng Junhong Han Qing Zhu |
| author_facet | Qunli Xiong Ying Zhou Su Zhang Yaguang Zhang Yongfeng Xu Yang Yang Congya Zhou Zhu Zeng Junhong Han Qing Zhu |
| author_sort | Qunli Xiong |
| collection | DOAJ |
| description | Abstract Background Members of the nuclear receptor‐binding SET domain (NSD) family of histone H3 lysine 36 methyltransferases comprise NSD1, NSD2 (MMSET/WHSC1), and NSD3 (Wolf–Hirschhorn syndrome candidate 1‐like 1, WHSC1L1). While the expression of NSD genes is essential to normal biological processes and cancer, knowledge of their expression levels to prognosticate in cancer remains unclear. Methods We analyzed the expression patterns for NSD family genes across multiple cancer types and examined their association with clinical features and patient survival profiles. Next, we explored the association between NSD3 expression and described features of the tumor microenvironment (TME) in PAAD, a severe type of pancreatic cancer. In particular, we correlated promoter methylation levels for NSD3 with patient outcomes in PAAD. Finally, we explored the putative oncogenic roles for NSD3 using a series of experiments with pancreatic cancer cells. Results We report that the expression of NSD family members is correlated with clinical prognosis across multiple types of cancers. Also, we demonstrate that NSD3 variants are most prevalent among NSD genes across cancers we analyzed. Notably, when compared with NSD1 and NSD2, we find that NSD3 is prominently expressed, and its expression is significantly linked with clinical outcome in pancreatic cancer. Furthermore, NSD3 is frequently amplified, exhibits low promoter methylation, and is correlated with immune cell infiltration and enhanced proliferation of pancreatic cancer. Finally, we demonstrate that knockdown of NSD3 alters H3K36me2 methylation, downstream gene expression and EGFR/ERK signaling in pancreatic cancer cells. Conclusions We find that expression levels, the presence of genetic variants of NSD family genes, as well as their promoter methylation are correlated with clinical outcomes in cancer, including pancreatic cancer. Our in vitro experiments suggest that NSD3 may be relevant to gene expression regulation and growth factor signaling in pancreatic cancer. |
| first_indexed | 2024-03-13T08:56:43Z |
| format | Article |
| id | doaj.art-b16c1d384fa0487b9cdb22c745f5d691 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-13T08:56:43Z |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-b16c1d384fa0487b9cdb22c745f5d6912023-05-28T20:33:59ZengWileyCancer Medicine2045-76342023-05-01129109611097810.1002/cam4.5774NSD3, a member of nuclear receptor‐binding SET domain family, is a potential prognostic biomarker for pancreatic cancerQunli Xiong0Ying Zhou1Su Zhang2Yaguang Zhang3Yongfeng Xu4Yang Yang5Congya Zhou6Zhu Zeng7Junhong Han8Qing Zhu9Department of Abdominal Oncology, West China Hospital Sichuan University Chengdu ChinaDepartment of Abdominal Oncology, West China Hospital Sichuan University Chengdu ChinaResearch Laboratory of Cancer Epigenetics and Genomics, Department of General Surgery, Frontiers Science Center for Disease‐Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital Sichuan University Chengdu ChinaResearch Laboratory of Cancer Epigenetics and Genomics, Department of General Surgery, Frontiers Science Center for Disease‐Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital Sichuan University Chengdu ChinaDepartment of Abdominal Oncology, West China Hospital Sichuan University Chengdu ChinaDepartment of Abdominal Oncology, West China Hospital Sichuan University Chengdu ChinaDepartment of Radiation Oncology Shaanxi Provincial People's Hospital Xi'an ChinaDepartment of Abdominal Oncology, West China Hospital Sichuan University Chengdu ChinaResearch Laboratory of Cancer Epigenetics and Genomics, Department of General Surgery, Frontiers Science Center for Disease‐Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital Sichuan University Chengdu ChinaDepartment of Abdominal Oncology, West China Hospital Sichuan University Chengdu ChinaAbstract Background Members of the nuclear receptor‐binding SET domain (NSD) family of histone H3 lysine 36 methyltransferases comprise NSD1, NSD2 (MMSET/WHSC1), and NSD3 (Wolf–Hirschhorn syndrome candidate 1‐like 1, WHSC1L1). While the expression of NSD genes is essential to normal biological processes and cancer, knowledge of their expression levels to prognosticate in cancer remains unclear. Methods We analyzed the expression patterns for NSD family genes across multiple cancer types and examined their association with clinical features and patient survival profiles. Next, we explored the association between NSD3 expression and described features of the tumor microenvironment (TME) in PAAD, a severe type of pancreatic cancer. In particular, we correlated promoter methylation levels for NSD3 with patient outcomes in PAAD. Finally, we explored the putative oncogenic roles for NSD3 using a series of experiments with pancreatic cancer cells. Results We report that the expression of NSD family members is correlated with clinical prognosis across multiple types of cancers. Also, we demonstrate that NSD3 variants are most prevalent among NSD genes across cancers we analyzed. Notably, when compared with NSD1 and NSD2, we find that NSD3 is prominently expressed, and its expression is significantly linked with clinical outcome in pancreatic cancer. Furthermore, NSD3 is frequently amplified, exhibits low promoter methylation, and is correlated with immune cell infiltration and enhanced proliferation of pancreatic cancer. Finally, we demonstrate that knockdown of NSD3 alters H3K36me2 methylation, downstream gene expression and EGFR/ERK signaling in pancreatic cancer cells. Conclusions We find that expression levels, the presence of genetic variants of NSD family genes, as well as their promoter methylation are correlated with clinical outcomes in cancer, including pancreatic cancer. Our in vitro experiments suggest that NSD3 may be relevant to gene expression regulation and growth factor signaling in pancreatic cancer.https://doi.org/10.1002/cam4.5774cell proliferationimmune infiltrationNSD3nuclear receptor‐binding SET domainpancreatic cancerprognosis biomarker |
| spellingShingle | Qunli Xiong Ying Zhou Su Zhang Yaguang Zhang Yongfeng Xu Yang Yang Congya Zhou Zhu Zeng Junhong Han Qing Zhu NSD3, a member of nuclear receptor‐binding SET domain family, is a potential prognostic biomarker for pancreatic cancer Cancer Medicine cell proliferation immune infiltration NSD3 nuclear receptor‐binding SET domain pancreatic cancer prognosis biomarker |
| title | NSD3, a member of nuclear receptor‐binding SET domain family, is a potential prognostic biomarker for pancreatic cancer |
| title_full | NSD3, a member of nuclear receptor‐binding SET domain family, is a potential prognostic biomarker for pancreatic cancer |
| title_fullStr | NSD3, a member of nuclear receptor‐binding SET domain family, is a potential prognostic biomarker for pancreatic cancer |
| title_full_unstemmed | NSD3, a member of nuclear receptor‐binding SET domain family, is a potential prognostic biomarker for pancreatic cancer |
| title_short | NSD3, a member of nuclear receptor‐binding SET domain family, is a potential prognostic biomarker for pancreatic cancer |
| title_sort | nsd3 a member of nuclear receptor binding set domain family is a potential prognostic biomarker for pancreatic cancer |
| topic | cell proliferation immune infiltration NSD3 nuclear receptor‐binding SET domain pancreatic cancer prognosis biomarker |
| url | https://doi.org/10.1002/cam4.5774 |
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