Liu Xiaodan, Zheng Fumin, Gao Meihua, Wang Yuanfei, Lv Xiaofang, Cong Beibei, Wang Wanchun
School of Stomatology, Binzhou Medical University, Yantai, China.
Department of Oral Mucosal Diseases, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, China.
Front Oncol. 2025 May 22;15:1579282. doi: 10.3389/fonc.2025.1579282. eCollection 2025.
This study aims to explore the regulatory effect of abnormal expression of CD46 and TREM1 on LC3B and ATG5 and to provide new targets for the molecular mechanism and treatment of OSCC.
Human oral squamous cell carcinoma cells CAL-27 were selected for culture. For related research, the CD46 shRNA interference test, immunohistochemistry (IHC), flow cytometry, qRT-PCR detection, Western blot, and tumor-bearing animal models were used.
cell experiments showed that CD46 and TREM1 were highly expressed on the surface of OSCC cells, while the expression of LC3B and ATG5 was significantly decreased. Compared with the control group (SC-shRNA), the CD46 shRNA group could effectively reduce the expression of CD46 in OSCC cells and increase the expression of autophagy and apoptosis protein (<0.01). experiments showed that the tumor volume of the shRNA group was significantly smaller than that of the SC-shRNA group (<0.01), the expression of CD46 and TREM1 was decreased considerably, and the expression of LC3B and ATG5 was higher (<0.01).
OSCC cells have high expression of CD46 and TREM1, while low expression of LC3B and ATG5, and the autophagy apoptosis signal is weakened. Interfering with CD46 can up-regulate the expression of autophagy apoptosis genes, reduce the tumor inflammatory microenvironment, induce the apoptosis of OSCC cells, and inhibit the proliferation and metastasis of OSCC. This study provides a new idea for the mechanism and targeted therapy of OSCC and has important theoretical significance and clinical application value.
本研究旨在探讨CD46和触发受体表达分子1(TREM1)异常表达对微管相关蛋白1轻链3β(LC3B)和自噬相关蛋白5(ATG5)的调控作用,为口腔鳞状细胞癌(OSCC)的分子机制及治疗提供新靶点。
选用人口腔鳞状细胞癌细胞CAL-27进行培养。相关研究采用CD46短发夹RNA(shRNA)干扰试验、免疫组织化学(IHC)、流式细胞术、实时定量聚合酶链反应(qRT-PCR)检测、蛋白质免疫印迹法(Western blot)及荷瘤动物模型。
细胞实验表明,CD46和TREM1在OSCC细胞表面高表达,而LC3B和ATG5的表达显著降低。与对照组(SC-shRNA)相比,CD46 shRNA组可有效降低OSCC细胞中CD46的表达,并增加自噬和凋亡蛋白的表达(P<0.01)。动物实验表明,shRNA组的肿瘤体积明显小于SC-shRNA组(P<0.01),CD46和TREM1的表达显著降低,而LC3B和ATG5的表达较高(P<0.01)。
OSCC细胞中CD46和TREM1高表达,而LC3B和ATG5低表达,自噬凋亡信号减弱。干扰CD46可上调自噬凋亡基因的表达,减少肿瘤炎症微环境,诱导OSCC细胞凋亡,抑制OSCC的增殖和转移。本研究为OSCC的发病机制及靶向治疗提供了新思路,具有重要的理论意义和临床应用价值。