Postgraduate Program in Oral Science, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Department of Oral Diagnosis, School of Dentistry, University of Campinas (UNICAMP), Piracicaba, São Paulo, Brazil.
Oral Surg Oral Med Oral Pathol Oral Radiol. 2023 Apr;135(4):530-538. doi: 10.1016/j.oooo.2023.01.009. Epub 2023 Feb 1.
The aim of the present study was to investigate the role of SNAIL1, E-cadherin, and N-cadherin immunoexpression in oral tongue carcinogenesis. In addition, we evaluated in vitro the impact of silencing of the nuclear transcription factor SNAIL1 on the viability, apoptosis, proliferation, migration, and invasion of SCC-9 and HSC-3 cells.
Immunohistochemical analysis of SNAIL1, E-cadherin, and N-cadherin was carried out in 47 samples representing oral epithelial dysplasia (OED) and 41 oral tongue squamous cell carcinoma (OTSCC). The suppression of SNAIL1 expression was performed using shRNA-expression vectors in HSC-3 and SCC-9 cells to investigate in vitro the impact of SNAIL1 on proliferation, apoptosis, viability, migration, and invasion of SCC-9 and HSC-3 cells.
Significant differences were observed in the expression of SNAIL1, E-cadherin, and N-Cadherin between OTSCC and OED. A low membrane expression of E-cadherin was strongly associated with poor overall survival in patients with OTSCC (P < .05), but the association did not withstand the Cox multivariate survival analysis. SNAIL1 silencing played a key role in the suppression of epithelial-mesenchymal transition and inhibited migration and invasion of HSC-3 cells (P < .0001, P < .01, respectively). In SCC-9 cells, SNAIL1 silencing promoted a significant reduction in the proliferation (P < .0001) and invasion (P < .0001).
The epithelial-mesenchymal transition is present in different stages of oral tongue carcinogenesis, and SNAIL1 plays a key role in this process, although the underlying mechanisms still need to be elucidated. Thus, SNAIL1 might be a promising therapeutic target in OTSCC.
本研究旨在探讨 SNAIL1、E-钙黏蛋白和 N-钙黏蛋白免疫表达在口腔舌癌发生中的作用。此外，我们还评估了沉默核转录因子 SNAIL1 对 SCC-9 和 HSC-3 细胞活力、凋亡、增殖、迁移和侵袭的体外影响。
对 47 例口腔上皮异型增生（OED）和 41 例口腔舌鳞状细胞癌（OTSCC）标本进行 SNAIL1、E-钙黏蛋白和 N-钙黏蛋白免疫组织化学分析。使用 shRNA 表达载体抑制 SNAIL1 表达，以研究 SNAIL1 对 SCC-9 和 HSC-3 细胞增殖、凋亡、活力、迁移和侵袭的体外影响。
OTSCC 与 OED 之间 SNAIL1、E-钙黏蛋白和 N-Cadherin 的表达存在显著差异。E-钙黏蛋白的低膜表达与 OTSCC 患者总生存不良密切相关（P <.05），但 Cox 多变量生存分析未支持该关联。SNAIL1 沉默在抑制上皮-间质转化方面发挥了关键作用，并抑制了 HSC-3 细胞的迁移和侵袭（P <.0001，P <.01，分别）。在 SCC-9 细胞中，SNAIL1 沉默显著降低了增殖（P <.0001）和侵袭（P <.0001）。
上皮-间质转化存在于口腔舌癌发生的不同阶段，SNAIL1 在这一过程中发挥关键作用，尽管其潜在机制仍需阐明。因此，SNAIL1 可能是 OTSCC 的一个有前途的治疗靶点。
