Department of Otorhinolaryngology-Head and Neck Surgery, The Third People's Hospital, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
Department of Otorhinolaryngology-Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Dis Markers. 2019 Jan 14;2019:6716472. doi: 10.1155/2019/6716472. eCollection 2019.
Cancer bioinformatics has been used to screen possible key cancer genes and pathways. Here, through bioinformatics analysis, we found that high expression of diaphanous related formin 1 (DIAPH1) was associated with poor overall survival in head and neck squamous cell carcinoma and laryngeal squamous cell carcinoma (LSCC). The effect of DIAPH1 in LSCC has not been previously investigated. Therefore, we evaluated the expression, function, and molecular mechanisms of DIAPH1 in LSCC. Immunohistochemistry and western blot analysis confirmed the significant upregulation of DIAPH1 in LSCC. We used DIAPH1 RNA interference to construct two DIAPH1-knockdown LSCC cell lines, AMC-HN-8 and FD-LSC-1, and validated the knockdown efficiency. Flow cytometry data showed that DIAPH1 inhibited apoptosis. Further, western blot analysis revealed that DIAPH1 knockdown increased the protein levels of ATR, p-p53, Bax, and cleaved caspase-3, -8, and -9. Thus, DIAPH1 is upregulated in LSCC and may act as an oncogene by inhibiting apoptosis through the ATR/p53/caspase-3 pathway in LSCC cells.
癌症生物信息学已被用于筛选可能的关键癌症基因和途径。在这里，通过生物信息学分析，我们发现长丝蛋白 1（DIAPH1）的高表达与头颈部鳞状细胞癌和喉鳞状细胞癌（LSCC）的总生存率降低有关。DIAPH1 在 LSCC 中的作用尚未被研究过。因此，我们评估了 DIAPH1 在 LSCC 中的表达、功能和分子机制。免疫组织化学和 Western blot 分析证实 DIAPH1 在 LSCC 中显著上调。我们使用 DIAPH1 RNA 干扰构建了两个 DIAPH1 敲低的 LSCC 细胞系，即 AMC-HN-8 和 FD-LSC-1，并验证了敲低效率。流式细胞术数据表明 DIAPH1 抑制细胞凋亡。进一步的 Western blot 分析显示，DIAPH1 敲低增加了 ATR、p-p53、Bax 和 cleaved caspase-3、-8 和 -9 的蛋白水平。因此，DIAPH1 在 LSCC 中上调，可能通过 ATR/p53/caspase-3 通路抑制 LSCC 细胞中的细胞凋亡而发挥癌基因的作用。
