Since companion dogs have the same living environment as humans, they are a good animal model for the study of human diseases; this is especially true of canine spontaneous mammary tumours models. A better understanding of the natural history and molecular mechanisms of canine mammary tumour is of great significance in comparative medicine. Here, we collected canine mammary tumour cases and then assayed the clinical cases by pathological examination and classification by HE staining and IHC. miRNA‐497 family members (miR‐497, miR‐16, miR‐195 and miR‐15) were positively correlated with the breast cancer marker genes p63 and PTEN. Modulation of the expression of miR‐497 in the canine mammary tumour cell lines CMT1211 and CMT 7364 induced apoptosis and inhibited cell proliferation. Mechanistically, IRAK2 was shown to be a functional target of miR‐497 that affects the characteristics of cancer cells by inhibiting the activity of the NF‐κB pathway. Overall, our work reveals the miR‐497/IRAK2/NF‐κB axis as a vital mechanism of canine mammary tumour progression and suggests this axis as a target in breast cancer.

中文翻译：

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miR-497通过IRAK2/NF-κB轴诱导犬乳腺肿瘤细胞凋亡

由于伴侣犬与人类有着相同的生存环境，因此是研究人类疾病的良好动物模型；对于犬自发性乳腺肿瘤模型尤其如此。更好地了解犬乳腺肿瘤的自然病程和分子机制对于比较医学具有重要意义。在这里，我们收集了犬乳腺肿瘤病例，然后通过病理学检查和HE染色和IHC分类对临床病例进行了分析。miRNA-497 家族成员（miR-497、miR-16、miR-195 和 miR-15）与乳腺癌标志基因 p63 和 PTEN 呈正相关。调节犬乳腺肿瘤细胞系 CMT1211 和 CMT 7364 中 miR-497 的表达诱导细胞凋亡并抑制细胞增殖。从机制上讲，IRAK2 被证明是 miR-497 的功能靶点，它通过抑制 NF-κB 通路的活性来影响癌细胞的特征。总的来说，我们的工作揭示了 miR-497/IRAK2/NF-κB 轴是犬乳腺肿瘤进展的重要机制，并表明该轴是乳腺癌的靶点。