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.

Aging is a physiological change that leads to a decline in biological functions from metabolic stress. To investigate the effect of aging on mandibular bone formation, we created SAMP1/Klotho-deficient mice and performed micro-computed tomography (micro-CT) and histology analyses in 4-or 8 week-old SAMP1/kl -/- mice. SAMP1/kl -/- mice exhibited extensive inflammation, tissue calcification, and abnormal mandibular bone development. Using micro-CT analysis, SAMP1/kl -/- mice displayed a loss of incisor roots and irregular dentinal tubule formation, as well as calcification within the pulp root canal. Furthermore, the mandibular ramus showed extensive ground glass appearance in SAMP1/kl -/- mice. In histological analysis, we found calcified skeletal structures and dysplastic bone formation in SAMP1/kl -/- mice. These results provide an understanding of the pathologic alterations of aging-related mandibular bone. SAMP1/kl -/- mice may serve as a novel model for dysosteogenesis in mandibular bone development.