Syntaxin-6(STX6),一种囊泡转运蛋白,是抑癌基因P53的直接靶标,支持肿瘤生长依赖于P53。然而,STX6在肿瘤微环境中的功能尚未见报道。在这项研究中,我们通过结合多个数据库的数据,全面探讨了癌基因STX6在泛癌症中的作用,包括癌症基因组图谱,CPTAC,cBioPortal,和定时器。然后,我们通过一系列体内外实验验证了STX6在肝细胞癌(HCC)和结直肠癌(CRC)中的致癌作用。生物信息学分析表明,STX6是几种癌症的癌基因,主要参与细胞周期,上皮-间质转化,氧化磷酸化,和肿瘤免疫调节,特别是肿瘤相关成纤维细胞(CAFs)和NKT细胞。此外,高水平的STX6可能表明患者对免疫疗法耐药。我们自己的数据表明,STX6水平在HCC和CRC中上调。敲低STX6水平可以阻滞细胞周期,抑制细胞增殖,迁移,和入侵。RNA-seq表明STX6显著参与癌症通路,如MAPK信号通路。在老鼠模型中,STX6敲低抑制肿瘤生长并增强抗PD-1功效。鉴于STX6在癌变和癌症免疫学中的重要作用,它有可能成为预测的生物标志物和癌症免疫治疗的靶点.
Syntaxin-6 (STX6), a vesicular transport protein, is a direct target of the tumor suppressor gene P53, supporting cancer growth dependent on P53. However, STX6\'s function in the tumor microenvironment has yet to be reported. In this research, we comprehensively explored the role of the oncogene STX6 in pan-cancer by combining data from several databases, including the Cancer Genome Atlas, CPTAC, cBioPortal, and TIMER. Then, we verified the carcinogenic effect of STX6 in hepatocellular carcinoma (HCC) and colorectal cancer (CRC) through a series of experiments in vitro and in vivo. Bioinformatics analysis demonstrated that STX6 is an oncogene for several cancers and is mainly involved in the cell cycle, epithelial-mesenchymal transition, oxidative phosphorylation, and tumor immune modulation, especially for tumor-associated fibroblasts (CAFs) and NKT cells. Additionally, a high level of STX6 could indicate patients\' resistance to immunotherapy. Our own data indicated that the STX6 level was upregulated in HCC and CRC. Knockdown of the STX6 levels could arrest the cell cycle and restrain cell proliferation, migration, and invasion. RNA-seq indicated that STX6 was significantly involved in pathways for cancer, such as the MAPK signal pathway. In a mouse model, knockdown of STX6 inhibited tumor growth and potentiated anti-PD-1 efficacy. In light of the essential roles STX6 plays in carcinogenesis and cancer immunology, it has the potential to be a predictive biomarker and a target for cancer immunotherapy.