Patients with oral squamous cell carcinoma (OSCC) generally have an elevated expression of homeobox C6 (HOXC6) gene. We found that HOXC6 was the significantly upregulated gene in hypopharyngeal squamous cell carcinoma (FaDu) cells using RNA-seq analysis. However, it remains unclear whether HOXC6 plays a role in tumor process mechanism. Our study aimed to explore the potential oncogenic role and the detailed molecular mechanism of HOXC6 in FaDu cells. In this study, Sirt1 was validated to be overexpressed in FaDu cells and associated with HOXC6 expression. Overexpression of HOXC6 promoted the cell colony formation, whereas inhibition of Sirt1 by Sirt1 inhibitor EX527 reduced cell proliferation/colony formation and migration, and induced apoptosis in HOXC6 overexpressed FaDu cells. Interestingly, mechanistic study showed that EX527 mediated Sirt1 suppression led to decreased HOXC6 expression and upregulation of Sirt1 significantly increased the expression of HOXC6. HOXC6 was shown to cooperate with Sirt1 to enhance cell survival. We propose that HOXC6 promotes cell growth/colony formation, and that the HOXC6 may be a progression of hypopharyngeal carcinoma by activating Sirt1 pathways.
SOCS3, a suppressor of cytokine signaling 3, is known as a negative regulator of various cytokines and a tumor suppressor gene in human tumors. This study aimed to investigate the role of SOCS3 in oral squamous cell carcinoma (OSCC) and its impact on epithelial-mesenchymal transition (EMT) in OSCC cells. Although SOCS3 is recognized as a negative regulator of various cytokines and a tumor suppressor gene in human tumors, its specific effects on OSCC remain poorly understood.
For the assessment of SOCS3 expression in OSCC, the UALCAN website and TCGA data were used to evaluate its expression in head and neck cancer. Additionally, immunohistochemical staining was conducted to determine the SOCS3 expression specifically in OSCC. The findings indicated a significant decrease in SOCS3 expression in tumor tissue compared to that in normal tissues.
To investigate the enhancement of SOCS3 expression in OSCC cancer cell lines, IL6 treatment was administered to MC3 cells. However, no significant differences were observed in cell viability, wound healing assay, and invasion assay. Conversely, the transfection of SOCS3 siRNA into OSCC cells led to a notable increase in cell viability and statistically significant increases in wound healing and invasion assays. These results suggest that SOCS3 plays a crucial role in cell viability and EMT in OSCC, thereby contributing to oral carcinogenesis. Further research is necessary to elucidate the precise role of SOCS3 in OSCC.