Department of Stomatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Sci Rep. 2024 Nov 6;14(1):26881. doi: 10.1038/s41598-024-78391-6.
This study first investigated how FNDC5 affected the development of oral cancer and revealed the role of FNDC5 in the migration and invasion of oral cancer. The present work evaluated differential FNDC5 expression within oral cancer samples versus matched non-carcinoma samples based on GEO database analysis and immunohistochemistry. We then generated oral cancer cell lines with FNDC5 overexpression and knockdown to determine the role of altered FNDC5 expression in the migration and invasion of oral cancer. PI3K inhibitor was used for investigating the possible mechanism underlying FNDC5 during EMT of oral cancer. Finally, these in-vitro results were validated using the lung metastatic nude mouse model. According to our results, FNDC5 level markedly decreased within oral cancer compared with adjacent samples and FNDC5 overexpression inhibited migration, invasion as well as EMT of oral cancer, while FNDC5 knockdown promoted oral cancer cell EMT. In addition, PI3K inhibitors blocked the induction of oral cancer cells EMT by FNDC5 knockdown. In vivo experiments further demonstrated the above results. This work is the first to illustrate the impact of FNDC5 on inhibiting migration and invasion of oral cancer, and our results suggest that FNDC5 affects EMT of oral cancer via the inhibition of PI3K/Akt/Snail pathway.
本研究首先探讨了 FNDC5 如何影响口腔癌的发展，并揭示了 FNDC5 在口腔癌迁移和侵袭中的作用。本工作基于 GEO 数据库分析和免疫组织化学评估了 FNDC5 在口腔癌样本与匹配的非癌样本中的差异表达。然后，我们通过过表达和敲低 FNDC5 生成了口腔癌细胞系，以确定 FNDC5 表达改变在口腔癌迁移和侵袭中的作用。使用 PI3K 抑制剂来研究 FNDC5 在口腔癌 EMT 过程中的潜在机制。最后，使用肺转移裸鼠模型验证了这些体外结果。根据我们的结果，FNDC5 在口腔癌中的水平明显低于相邻样本，FNDC5 过表达抑制了口腔癌的迁移、侵袭和 EMT，而 FNDC5 敲低促进了口腔癌细胞 EMT。此外，PI3K 抑制剂阻断了 FNDC5 敲低诱导的口腔癌细胞 EMT。体内实验进一步验证了上述结果。这项工作首次阐明了 FNDC5 对抑制口腔癌迁移和侵袭的影响，我们的结果表明，FNDC5 通过抑制 PI3K/Akt/Snail 通路影响口腔癌的 EMT。
