Wang Rongrong, Zhu Chuyang, Yuan Xiaoyue, Zhu Cuipeng, Adam Saber Y, Liu Haoyu, Cai Demin, Liu Jiaguo
MOE 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, China.
Alovet Co., Ltd., Suzhou 215021, China.
Animals (Basel). 2025 Aug 4;15(15):2274. doi: 10.3390/ani15152274.
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.
核受体参与多种生物学过程，其中RORγ可调节炎症相关基因的表达，因此常被用作癌症的治疗靶点。犬乳腺癌是犬类最常见的肿瘤疾病之一，在过去五年中，中国犬乳腺肿瘤（CMT）的相对发病率为46.71%，严重威胁犬类的生命健康。因此，寻找针对犬乳腺癌的新型药物具有重要意义。本研究旨在探讨RORγ抑制剂W6134和XY018如何通过组蛋白修饰影响CMT-N7细胞中炎症基因的表达。这些结果表明，W6134和XY018可上调与炎症和凋亡相关的信号通路，并影响相关基因的表达。RORγ与炎症相关基因之间的密切联系进一步证实，RORγ可能是犬类癌症的治疗靶点。此外，采用染色质免疫沉淀-定量聚合酶链反应（ChIP-qPCR）检测组蛋白标记物如P300、H3K27ac、H3K4me1、H3K9la和H3K9bhb在CXCL10和MECOM基因靶位点的富集情况。总的来说，我们的研究结果为RORγ在犬乳腺癌中的保护作用提供了分子证据，可能是通过组蛋白修饰调节炎症通路，为提高患病犬的治愈率和生存率提供了新的见解。
