Background
Lymph node metastasis is one of the most important factors affecting the prognosis of tongue cancer, and the molecular mechanism regulating lymph node metastasis of tongue cancer is poorly known.
Conclusion
Our study demonstrated that IER3 plays important roles in lymphangiogenesis regulation and prognosis in tongue cancer and might be a potential therapeutic target.
Methods
The gene expression dataset GSE2280 and The Cancer Genome Atlas (TCGA) tongue cancer dataset were downloaded. R software was used to identify the differentially expressed hallmark gene sets and individual genes between metastatic lymph node tissues and primary tongue cancer tissues, and the Kaplan-Meier method was used to evaluate the association with overall survival. The screening and validation of functional genes was performed using western blot, q-PCR, CCK-8, migration and invasion assays, and lymphangiogenesis was examined by using a tube formation assay.
Results
Thirteen common hallmark gene sets were found based on Gene Set Variation Analysis (GSVA) and then subjected to differential gene expression analysis, by which 76 deregulated genes were found. Gene coexpression network analysis and survival analysis further confirmed that IER3 was the key gene associated with the prognosis and lymph node metastasis of tongue cancer patients. Knockdown of IER3 with siRNA inhibited the proliferation, colony formation, migration and invasion of Tca-8113 cells in vitro and it also inhibited the secretion and expression of VEGF-C in these cells. The culture supernatant of Tca-8113 cells could promote lymphangiogenesis and migration of lymphatic endothelial cells, and knockdown of IER3 in Tca-8113 cells suppressed these processes.