Functional analysis of the miR-145/Fascin1 cascade in canine oral squamous cell carcinoma
Functional analysis of the miR-145/Fascin1 cascade in canine oral squamous cell carcinoma
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DOI：
10.1111/odi.14143
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发表时间：
2022-02-13
期刊：
影响因子：
3.8
通讯作者：
Matsui, Asuka
中科院分区：
文献类型：
--
作者：
Noguchi, Shunsuke;Tanimoto, Nanami;Matsui, Asuka
目的犬口腔鳞状细胞癌（SCC）好发于牙龈和扁桃体。犬口腔鳞状细胞癌的生物学行为与人头颈部鳞状细胞癌（HNSCC）相似。抑制侵袭和转移对于治疗犬和人HNSCC是非常重要的。本研究探讨microRNA（miR）-145和Fascin 1（FSCN 1）在犬口腔鳞癌侵袭中的意义。材料与方法采用实时荧光定量PCR和免疫组化方法检测犬口腔鳞癌组织和细胞系中miR-145和FSCN 1的表达。犬口腔SCC细胞系用于体外测定。结果犬口腔鳞癌组织中miR-145表达下调，FSCN 1 mRNA表达上调。免疫组化显示，FSCN 1在SCC中的表达较正常黏膜明显上调。用miR-145或FSCN 1 siRNA转染犬SCC细胞通过抑制上皮向间充质转化抑制细胞生长并减弱细胞迁移以及侵袭。此外，miR-145的启动子区域在SCC细胞系和组织中高度甲基化。结论miR-145在犬口腔鳞状细胞癌中的表达与功能与人口腔鳞状细胞癌相似。因此，犬口腔鳞状细胞癌可能代表了一个有价值的人类HNSCC的临床前模型。
Objectives Canine oral squamous cell carcinoma (SCC) often develops in the gingiva and tonsils. The biological behavior of canine oral SCC is similar to that of human head and neck SCC (HNSCC). Inhibiting invasion and metastasis is major importance for the treatment of canine and human HNSCC. In this study, the significance of microRNA (miR)-145 and Fascin1 (FSCN1) in the invasion of canine oral SCC was explored. Materials and methods Canine oral SCC tissues and cell lines were used for miR-145 and FSCN1 expression analysis via real-time PCR and immunohistochemistry. Canine oral SCC cell lines were used for in vitro assays. Results miR-145 was downregulated while FSCN1 mRNA was upregulated in canine oral SCC. Immunohistochemistry revealed that FSCN1 was upregulated in SCC when compared to normal mucosa. Transfection of canine SCC cells with miR-145 or FSCN1 siRNA suppressed cell growth and attenuated cell migration as well as invasion by inhibiting the epithelial-to-mesenchymal transition. Furthermore, the promoter region of miR-145 was highly methylated in SCC cell lines and tissues. Conclusion The expression profile and functions of miR-145 in canine oral SCC are similar to those in human HNSCC. Thus, canine oral SCC may represent a valuable preclinical model for human HNSCC.