Abstract
The diaphanous related formin 1 (DIAPH1) protein is involved in the regulation of dynamic cytoskeleton reorganization, which is closely related to mitosis and the cell cycle. Cell cycle disorders are generally regarded as important underlying causes of many cancers. In the current study, we have revealed that DIAPH1 expression is an independent prognostic factor for overall survival in patients with laryngeal squamous cell carcinoma (LSCC) and that DIAPH1 promotes colony formation, cell proliferation, and G1/S progression in LSCC cells. Additionally, DIAPH1 promotes growth of AMC-HN-8 LSCC-derived tumors in vivo. In this study, RNA-sequencing analysis revealed that DIAPH1 knockdown led to changes in the expression of genes associated with signaling during the cell cycle. Using western blot analyses, we further demonstrated that DIAPH1 knockdown resulted in upregulation of p21Waf1/Cip1, p19Ink4d, p27Kip1, and p16Ink4a and downregulation of cyclinA2, cyclinD1, CDK2, CDK4, and CDK6. These results suggest that DIAPH1 influences the expression of genes in several signaling pathways and promotes LSCC progression by regulating the cell cycle.
Highlights
Laryngeal squamous cell carcinoma (LSCC), accounting for more than 95% of all laryngeal carcinomas [1], is a common type of malignant tumor in the head and neck region
Using 36 paired LSCC and matching adjacent non-tumor tissues, we previously showed that expression of the protein diaphanous related formin 1 (DIAPH1, termed mDia1), a member of the formin family, is significantly upregulated in LSCC tissues
IHC analysis of 126 patients showed that DIAPH1 protein expression was significantly upregulated in patients with high T stage, lymph node metastasis, later clinical-stage, or supraglottic or subglottic LSCC (Table 2, Figure 1B)
Summary
Laryngeal squamous cell carcinoma (LSCC), accounting for more than 95% of all laryngeal carcinomas [1], is a common type of malignant tumor in the head and neck region. Based on cancer statistics from the National Central Cancer Registry of China, it was estimated that 26,400 new cases of laryngeal carcinoma and 14,500 cancer deaths were due to laryngeal carcinoma in China in 2015 [2]. Siegel previously reported of the approximately 12,410 cases diagnosed with laryngeal carcinoma in the United States in 2019, 3,760 would lead to deaths [3]. The search for new diagnostic and therapeutic targets for laryngeal cancer, especially for LSCC, has become more pressing.
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