RNA结合蛋白UPF1沉默CEBPA-AS1提高口腔鳞癌化疗敏感性和微环境免疫活性的分子机制及应用研究

口腔鳞癌是头颈部区域最常见的恶性肿瘤,联合免疫和化学治疗可提高抗肿瘤治疗效果。我们前期研究发现沉默长链非编码RNA CEBPA-AS1能提高口腔鳞癌化疗敏感性和微环境免疫活性。但其参与的具体免疫调控机制尚不清楚。因此提出本科研假说：CEBPA-AS1既能在口腔鳞癌细胞内诱导微环境中免疫细胞死亡，又能通过外泌体途径转运到达树突细胞并抑制其免疫活性；RNA结合蛋白UPF1-FDa肽段靶向肿瘤细胞并结合CEBPA-AS1，综合提高口腔鳞癌的治疗效果。具体研究内容：①CEBPA-AS1在口腔鳞癌细胞内诱导免疫细胞死亡的作用机制；②CEBPA-AS1通过外泌体途径抑制免疫活性的分子机制；③UPF1-FDa肽段靶向肿瘤细胞，提高口腔鳞癌化疗和免疫治疗的协同效应。本项目旨在明确RNA结合蛋白整合化学治疗和免疫治疗对口腔鳞癌的作用和临床应用前景，为口腔鳞癌的临床综合治疗提供新策略和新靶点。

Oral squamous cell carcinoma is the most common malignant tumor in the head and neck region. Combination of immunotherapy and chemotherapy can improve the antineoplastic effect. Previous studies have shown that silencing long-chain non-coding RNA CEBPA-AS1 can improve chemo-sensitivity and microenvironment immunity of oral squamous cell carcinoma. However, the specific immune regulatory mechanisms involved are still unclear. Therefore, it is proposed that CEBPA-AS1 can not only induce the death of immune cells in the microenvironment of oral squamous cell carcinoma cells, but also transport to dendritic cells through exosome pathway and inhibit their immune activity. RNA binding protein UPF1-FDa peptide segment targeting tumor cells and combining with CEBPA-AS1 can comprehensively improve the therapeutic effect of oral squamous cell carcinoma. Specific research contents: 1) The mechanism of CEBPA-AS1 inducing immune cell death in oral squamous cell carcinoma cells; 2) the molecular mechanism of CEBPA-AS1 inhibiting immune activity through exosome pathway; 3) UPF1-FDa peptide targeting cancer cells to enhance the synergistic effect of chemotherapy and immunotherapy for oral squamous cell carcinoma. The aim of this project is to clarify the role and clinical application prospects of RNA-binding protein integrative chemotherapy and immunotherapy in oral squamous cell carcinoma, and to provide new strategies and targets for clinical comprehensive treatment of oral squamous cell carcinoma.