Aberrant overexpression of transcription factor Forkhead box D1 predicts poor prognosis and promotes cancer progression in HNSCC

Abstract

Objectives Forkhead box D1, the core transcription factor member of FOX family, has gradually seen as a key cancerous regulatory. However, its expression and carcinogenicity in head and neck squamous cell carcinoma (HNSCC) have not been reported yet. This study was to investigate its expression pattern, clinicopathological significance and biological roles in HNSCC. Methods HNSCC data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to indicate the detailed expression pattern and outcome association of FOXD1, while Western Blot assay to detect FOXD1 level in a panel of HNSCC cell lines as well as immunocytochemistry to explore FOXD1 protein abundance and sublocation. Series of siRNA-mediated FOXD1 knock-down experiments to assess the proliferation, migration, invasion and anti- apoptosis ability after FOXD1 down-regulation. Bioinformatic analysis to find out which biological function and cancer-related pathways of FOXD1 associated genes involved in. Results FOXD1 mRNA was significantly overexpressed in TCGA-HNSCC, GSE6631, GSE12452, GSE25099 and GSE30784. Besides, IHC results shown that nuclear location FOXD1 protein was significantly higher in primary HNSCC specimens from cohort involved in this study. Also, FOXD1 abundance was significantly correlated with cervical node metastasis and poor over-all/disease-free survival after combination analysis with patient pathological information. siRNA-mediated FOXD1 knock-down significantly inhibited cell proliferation, migration and invasion and induced apoptosis in HNSCC cells. Further analysis of GSEA, GO and KEGG showed that FOXD1 expression was significantly associated with oncological function and cancer-related pathways. Conclusions Taken together, our study implies that the potential oncogene, FOXD1, facilitates oncological behavior who can be identified as a brand-new HNSCC biomarker with diagnostic and prognostic significance.

Decoding the IGF1 Signaling Gene Regulatory Network Behind Alveologenesis from A Mouse Model of Bronchopulmonary Dysplasia

“…The signaling of FGF10 and the expression of Wnt5a and Foxd1 were blocked in culture with the FGFR inhibitor (Infigratinib at 1uM as in Manchado et al, 2016; Nakamura et al, 2015; Wong et al, 2018), siWnt5a (at 20nM as in Nemoto et al, 2012; Sakisaka et al, 2015; Zhao et al, 2017) and siFoxd1 (at 20nM as in Li et al, 2021; Nakayama et al, 2015; Wu et al, 2018) respectively, and their effects on other SCMF genes were quantified by RT-PCR (Fig.4C). Identified genes with significant change are designated as targets of the gene/pathway perturbed, and their connections are plotted on the network (Fig.4D).…”

Decoding the IGF1 signaling gene regulatory network behind alveologenesis from a mouse model of bronchopulmonary dysplasia

“…The signaling of FGF10 and the expression of Wnt5a and Foxd1 were blocked in culture with the FGFR inhibitor (Infigratinib at 1 uM as in Manchado et al, 2016 ; Nakamura et al, 2015 ; Wong et al, 2018 ), siWnt5a (at 20 nM as in Nemoto et al, 2012 ; Sakisaka et al, 2015 ; Zhao et al, 2017 ), and siFoxd1 (at 20 nM as in Li et al, 2021 ; Nakayama et al, 2015 ; Wu et al, 2018 ), respectively, and their effects on other SCMF genes were quantified by RT-PCR ( Figure 4C ). Identified genes with significant change are designated as targets of the gene/pathway perturbed, and their connections are plotted on the network ( Figure 4D ).…”

The Prognostic Significance of FOXD1 Expression in Head and Neck Squamous Cell Carcinoma

“…This phenomenon is consistent with previous studies. Huang et al and Li et al found that FOXD1 was highly expressed in carcinoma tissues, and this high expression turned out to be the independent prognostic factors that had a significant relationship with the survival of patients [ 28 , 29 ]. Different from what Li et al had demonstrated [ 30 ], we noted that the expression of FOXD1 was not statistically related to advanced TNM stage and N+ status, but a high expression of FOXD1 was correlated with recurrence or metastasis.…”