海南医学院学报2024,Vol.30Issue(10):769-778,10.DOI:10.13210/j.cnki.jhmu.20240313.001
ATP2A1影响结直肠癌增殖、迁移及免疫浸润的机制研究
ATP2A1 regulates proliferation and migration in colorectal cancer and serves as a predictor of patient prognosis and immune infiltration
摘要
Abstract
Objective:To investigate the mechanism of endoplasmic reticulum Ca2+-translocating ATPase isoform 1(ATP2A1)involved in influencing the biological behavior and immune infiltration of colorectal cancer(CRC).Methods:Tran-scriptome and immunohistochemistry(IHC)were used to analyze the relationship between ATP2A1 expression in colorectal can-cer tumors and the prognosis of colorectal cancer patients,and GO and KEGG were used to analyze the cellular functions and sig-naling pathways that may be involved in the expression level of ATP2A1.The ESTIMATE algorithm was used to analyze the ef-fect of ATP2A1 expression on the tumor microenvironment and the mutational load of tumors.The CCK8 proliferation assay and flow cell cycle assay were used to detect the mechanism of ATP2A1 involved in colorectal cancer proliferation,and the mechanism of ATP2A1 involved in colorectal cancer migration was analyzed by using scratch wound healing assay,Transwell assay and West-ern blot assay.Results:Colorectal cancer patients were divided into two groups of high and low expression based on the median val-ue of ATP2A1 expression.Kaplan-Meier curves and Cox regression analyses demonstrated that high ATP2A1 expression was a prognostic risk factor for colorectal cancer patients,and the results of the ESTIMATE algorithm demonstrated that ATP2A1 ex-pression decreased the abundance of immune cell infiltration,increased the tumor mutational load(TMB)and tumor cell stem-ness.The results of CCK8 proliferation assay and cell cycle assay showed that knockdown of ATP2A1 expression caused S-phase blockage in rectal cancer cells and thus inhibited cell proliferation.The results of scratch wound healing assay,Transwell and West-ern blot assay showed that ATP2A1 could enhance the migration ability of colorectal cancer cells by promoting epithelial mesen-chymal transition of colorectal cancer cells.Conclusion:ATP2A1 is highly expressed in colorectal cancer,which can promote the proliferation and migration of colorectal cancer cells,and affect the prognosis and immunotherapeutic efficacy of colorectal cancer patients.关键词
ATP2A1/结直肠癌/免疫浸润/上皮间质转化Key words
Colorectal cancer/ATP2A1/Immune infiltration/EMT分类
医药卫生引用本文复制引用
董锐,张富星,武心悦,倪郅楷,吴华彰,刘牧林..ATP2A1影响结直肠癌增殖、迁移及免疫浸润的机制研究[J].海南医学院学报,2024,30(10):769-778,10.基金项目
This study was supported by Natural Science Project of Anhui Province(2108085MH291) (2108085MH291)
Bengbu Medical College Graduate Research Innovation Project(Byycx22123) 安徽省自然科学项目(2108085MH291) (Byycx22123)
蚌埠医学院研究生科研创新项目(Byycx22123) (Byycx22123)