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Abstract：
To analyze the mechanism of how interfering with the cytokeratin 19 (CK19) pathway via the ferroptosis pathway affects tumor biological behaviors in the process of oral squamous cell carcinoma (OSCC) development. TCGA was used to analyze the expression of CK19 in pan-cancer and head and neck squamous cell carcinoma (HNSC) and to explore the ferroptosis-related genes related to HNSC. The effect of silencing CK19 on the migration ability of HSC-4 cells was verified by wound healing and migration assay. HSC-4 cells with silencing of CK19 and tumor-bearing nude mouse model were constructed. RT-qPCR, immunofluorescence and western blot were used to analyze the expression of ferroptosis-related genes. CK19 is highly expressed in human OSCC and nude mice. The migration ability of cells in the CK19-silenced group was lower than that of the control group. In vivo and in vitro, CK19 was negatively correlated with the expression of ACSL4 and positively correlated with the expression of GPX4. Compared with the control group, GPX4 expression was down-regulated and ACSL4 expression was up-regulated in the CK19-silenced group. Silencing CK19 also increased intracellular Fe2+ content and MDA content. Silencing CK19 can affect the expression of GPX4 and ACSL4 to regulate ferroptosis and at the same time increase the content of MDA, Fe2+ and ROS levels, thereby activating the regulation of ferroptosis pathway in the development of OSCC.
摘要：
分析在口腔鳞状细胞癌（OSCC）发生发展过程中，通过铁凋亡途径干扰细胞角蛋白19（CK19）途径影响肿瘤生物学行为的机制。用TCGA分析CK19在泛癌症和头颈部鳞状细胞癌(HNSC)中的表达,并探讨与HNSC相关的铁凋亡相关基因。通过伤口愈合和迁移实验验证沉默CK19对HSC-4细胞迁移能力的影响。建立沉默CK19的HSC-4细胞和荷瘤裸鼠模型。RT-qPCR,免疫荧光和蛋白质印迹分析铁凋亡相关基因的表达。CK19在人OSCC和裸鼠中高表达。CK19沉默组细胞的迁移能力低于对照组。体内和体外，CK19与ACSL4的表达呈负相关，与GPX4的表达呈正相关。与对照组相比,CK19沉默组GPX4表达下调,ACSL4表达上调。沉默CK19也增加了细胞内Fe2+含量和MDA含量。沉默CK19可以影响GPX4和ACSL4的表达以调节铁凋亡，同时增加MDA含量，Fe2+和ROS水平，从而激活铁凋亡通路在OSCC发展中的调控。
