Zhang Weiwei, Bai Xueyan, Liu Tingting, Mao Yulong, Zhang Lingnan, Wang Wenlong, Yu Huanying
Department of Orthodontics, Binzhou Medical University Hospital, Binzhou, China.
Department of Oral Medicine, Binzhou Medical University Hospital, Binzhou, China.
J Dent Sci. 2024 Oct;19(4):2268-2277. doi: 10.1016/j.jds.2024.02.015. Epub 2024 Feb 29.
BACKGROUND/PURPOSE: Rho GTPase activating protein 11A (ARHGAP11A) can facilitate GTP hydrolysis in RhoA. The functions of ARHGAP11A in oral squamous cell carcinoma (OSCC) have not yet been explored. This study aimed to investigate the expression profile of ARHGAP11A in OSCC, its correlation with patient prognosis, its effect on cell-cycle progression, and the mechanisms by which it is dysregulated.
Bioinformatics analysis was conducted using data from The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma (TCGA-HNSC). Lentiviruses carrying shRNAs were employed to determine the effects of knockdown on tumor cell proliferation and cell-cycle progression. Dual-luciferase reporter assays were utilized to examine how FOXM1 transcriptionally regulates expression.
upregulation was associated with unfavorable overall survival (OS) in patients with TSCC (HR: 2.142, 95%CI: 1.224-3.749, = 0.007), but not in patients with OSCC of sites other than the tongue. knockdown inhibited the proliferation of TSCC cells and , and induced G1 phase arrest. knockdown increased GTP-RhoA but decreased p-RB levels, while it did not affect the total expression of RhoA and RB. knockdown increased p27 and decreased cyclin E1 expression. is transcriptionally activated by FOXM1 via multiple FOXM1 binding sites in the promoter regions in TSCC cells.
This study revealed the oncogenic role of ARHGAP11A in TSCC, highlighting its impact on cell-cycle control and tumor proliferation. Furthermore, the regulatory relationship between FOXM1 and ARHGAP11A provides new insights into the transcriptional networks in TSCC.
背景/目的：Rho GTP酶激活蛋白11A（ARHGAP11A）可促进RhoA中的GTP水解。ARHGAP11A在口腔鳞状细胞癌（OSCC）中的功能尚未得到探索。本研究旨在调查ARHGAP11A在OSCC中的表达谱、其与患者预后的相关性、其对细胞周期进程的影响以及其失调的机制。
使用来自癌症基因组图谱-头颈部鳞状细胞癌（TCGA-HNSC）的数据进行生物信息学分析。携带短发夹RNA的慢病毒用于确定敲低对肿瘤细胞增殖和细胞周期进程的影响。双荧光素酶报告基因检测用于检查FOXM1如何转录调节表达。
上调与舌鳞状细胞癌（TSCC）患者的不良总生存期（OS）相关（HR：2.142，95%CI：1.224 - 3.749，P = 0.007），但在舌以外部位的OSCC患者中无相关性。敲低抑制了TSCC细胞CAL27和SCC9的增殖，并诱导G1期阻滞。敲低增加了GTP-RhoA但降低了p-RB水平，而它不影响RhoA和RB的总表达。敲低增加了p27并降低了细胞周期蛋白E1的表达。在TSCC细胞中，FOXM1通过启动子区域中的多个FOXM1结合位点转录激活ARHGAP11A。
本研究揭示了ARHGAP11A在TSCC中的致癌作用，突出了其对细胞周期控制和肿瘤增殖的影响。此外，FOXM1与ARHGAP11A之间的调控关系为TSCC中的转录网络提供了新的见解。
