Abstract
BackgroundLymph 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.MethodsThe 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.ResultsThirteen 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.ConclusionOur study demonstrated that IER3 plays important roles in lymphangiogenesis regulation and prognosis in tongue cancer and might be a potential therapeutic target.
Highlights
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
We investigated the roles of IER3 in tongue cancer cells by performing proliferation, migration and invasion assays, and we demonstrated that IER3 could promote lymphangiogenesis in vitro
Analysis of hallmark gene sets involved in lymph node metastasis Hallmark gene sets consist of fifty sets that represent over four thousands original overlapping gene sets from v4.0 MSigDB collections C1 to C6, and provide accurate results when used with enrichment analysis methods in cancer [15]
Summary
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. Lymph node metastasis tends to occur during the early stage of tongue cancer, and it is one of the important factors leading to poor prognosis [3]. Lymph node metastasis during tumor progression involves the. Using bioinformatic techniques to mine and analyze microarrays and sequencing datasets can provide a new direction for studies on tumor development and progression. TCGA (The Cancer Genome Atlas) provides genomic sequencing datasets and clinical data for 33 types of cancer [11]. Both GEO and TCGA have made lasting contributions to understanding the mechanisms of cancer development and progression and have identified novel targets for cancer therapy [12]
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