A Small-Molecule Compound Targeting Canine Mammary Cancer Regulates CXCL10 and MECOM Transcripts via Histone Modifications in CMT-N7
Nuclear receptors are involved in multiple biological processes, among which RORγ can regulate the expression of inflammation-related genes and is thus frequently used as a therapeutic target for cancer. Canine mammary cancer is one of the most common tumor diseases in dogs, with a relative incidenc...
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2025-08-01
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| author | Rongrong Wang Chuyang Zhu Xiaoyue Yuan Cuipeng Zhu Saber Y. Adam Haoyu Liu Demin Cai Jiaguo Liu |
| author_facet | Rongrong Wang Chuyang Zhu Xiaoyue Yuan Cuipeng Zhu Saber Y. Adam Haoyu Liu Demin Cai Jiaguo Liu |
| author_sort | Rongrong Wang |
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| description | Nuclear receptors are involved in multiple biological processes, among which RORγ can regulate the expression of inflammation-related genes and is thus frequently used as a therapeutic target for cancer. Canine mammary cancer is one of the most common tumor diseases in dogs, with a relative incidence rate of 46.71% for CMT in China over the past five years, severely threatening the life and health of dogs. Therefore, the search for novel drugs targeting canine mammary cancer is of great significance. This study aims to investigate how the RORγ inhibitors W6134 and XY018 affect the expression of inflammatory genes through histone modifications in CMT-N7 cells. These results show that W6134 and XY018 can upregulate signaling pathways related to inflammation and apoptosis and influence the expression of associated genes. The close link between RORγ and inflammation-related genes further confirms that RORγ may serve as a therapeutic target for canine cancer. Additionally, ChIP-qPCR was used to detect the enrichment of histone markers such as P300, H3K27ac, H3K4me1, H3K9la, and H3K9bhb at the target loci of CXCL10 and MECOM genes. Collectively, our findings provide molecular evidence for the protective role of RORγ in canine mammary cancer, potentially by regulating inflammatory pathways via histone modifications, offering new insights for improving the cure rate and survival of affected dogs. |
| format | Article |
| id | doaj-art-0c0d00a1671e4124b543a4762d91800f |
| institution | Kabale University |
| issn | 2076-2615 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | MDPI AG |
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| series | Animals |
| spelling | doaj-art-0c0d00a1671e4124b543a4762d91800f2025-08-20T04:00:49ZengMDPI AGAnimals2076-26152025-08-011515227410.3390/ani15152274A Small-Molecule Compound Targeting Canine Mammary Cancer Regulates CXCL10 and MECOM Transcripts via Histone Modifications in CMT-N7Rongrong Wang0Chuyang Zhu1Xiaoyue Yuan2Cuipeng Zhu3Saber Y. Adam4Haoyu Liu5Demin Cai6Jiaguo Liu7MOE Joint International Research Laboratory of Animal Health and Food Safety and Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaJiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, ChinaJiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, ChinaJiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, ChinaJiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, ChinaJiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, ChinaJiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, ChinaMOE Joint International Research Laboratory of Animal Health and Food Safety and Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaNuclear receptors are involved in multiple biological processes, among which RORγ can regulate the expression of inflammation-related genes and is thus frequently used as a therapeutic target for cancer. Canine mammary cancer is one of the most common tumor diseases in dogs, with a relative incidence rate of 46.71% for CMT in China over the past five years, severely threatening the life and health of dogs. Therefore, the search for novel drugs targeting canine mammary cancer is of great significance. This study aims to investigate how the RORγ inhibitors W6134 and XY018 affect the expression of inflammatory genes through histone modifications in CMT-N7 cells. These results show that W6134 and XY018 can upregulate signaling pathways related to inflammation and apoptosis and influence the expression of associated genes. The close link between RORγ and inflammation-related genes further confirms that RORγ may serve as a therapeutic target for canine cancer. Additionally, ChIP-qPCR was used to detect the enrichment of histone markers such as P300, H3K27ac, H3K4me1, H3K9la, and H3K9bhb at the target loci of CXCL10 and MECOM genes. Collectively, our findings provide molecular evidence for the protective role of RORγ in canine mammary cancer, potentially by regulating inflammatory pathways via histone modifications, offering new insights for improving the cure rate and survival of affected dogs.https://www.mdpi.com/2076-2615/15/15/2274RORγcanine mammary cancerinflammationhistone modifications |
| spellingShingle | Rongrong Wang Chuyang Zhu Xiaoyue Yuan Cuipeng Zhu Saber Y. Adam Haoyu Liu Demin Cai Jiaguo Liu A Small-Molecule Compound Targeting Canine Mammary Cancer Regulates CXCL10 and MECOM Transcripts via Histone Modifications in CMT-N7 Animals RORγ canine mammary cancer inflammation histone modifications |
| title | A Small-Molecule Compound Targeting Canine Mammary Cancer Regulates CXCL10 and MECOM Transcripts via Histone Modifications in CMT-N7 |
| title_full | A Small-Molecule Compound Targeting Canine Mammary Cancer Regulates CXCL10 and MECOM Transcripts via Histone Modifications in CMT-N7 |
| title_fullStr | A Small-Molecule Compound Targeting Canine Mammary Cancer Regulates CXCL10 and MECOM Transcripts via Histone Modifications in CMT-N7 |
| title_full_unstemmed | A Small-Molecule Compound Targeting Canine Mammary Cancer Regulates CXCL10 and MECOM Transcripts via Histone Modifications in CMT-N7 |
| title_short | A Small-Molecule Compound Targeting Canine Mammary Cancer Regulates CXCL10 and MECOM Transcripts via Histone Modifications in CMT-N7 |
| title_sort | small molecule compound targeting canine mammary cancer regulates cxcl10 and mecom transcripts via histone modifications in cmt n7 |
| topic | RORγ canine mammary cancer inflammation histone modifications |
| url | https://www.mdpi.com/2076-2615/15/15/2274 |
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