Objectives: To investigate the role of Holliday cross-recognition protein (HJURP) in tumorigenesis, progression, and immunotherapy responses.
Methods: Bioinformatics approaches were used to analyze the expression level of HJURP in various cancers and its association with prognosis, clinical stage, and immune cell infiltration using TCGA, GTEx, SangerBox and TIMER 2.0 databases. LinkedOmics database was employed to investigate HJURP-related genes and their potential functions in kidney renal clear cell carcinoma (KIRC). The expression of HJURP in KIRC samples was examined with immunohistochemistry, Western blotting and qRT-PCR, and the effect of HJURP silencing on cell proliferation and migration was tested in cultured KIRC cells.
Results: HJURP was highly expressed in 26 cancers with negative correlations with the patients' survival outcomes in 5 cancers including KIRC (P<0.05). HJURP expression levels was strongly correlated with clinical stages and immune cell infiltration in the tumors. In KIRC, HJURP expression was significantly elevated (P<0.0001) and showed a positive correlation with TNM stage (P<0.05), overall stage (P<0.01) and immune cell infiltration. Gene Ontology (GO) functional analysis showed that HJURP is predominantly enriched in biological processes such as biological regulation and metabolic processes. Concerning cellular components, HJURP is primarily localized to the cell membrane and nucleus. In terms of molecular functions, it is chiefly enriched in activities related to protein binding and ion binding. HJURP was highly expressed in both clinical KIRC tissues and KIRC cell lines (P<0.001). In cultured KIRC cells, silencing of HJURP significantly inhibited cell proliferation and migration abilities.
Conclusions: HJURP may serves as an indicator of prognosis and immunotherapy response of KIRC, and its high expression enhances malignant behaviors of KIRC cells.
目的: 探讨Holliday交叉识别蛋白（HJURP）在肿瘤发生、进展及免疫治疗中的作用。方法: 采用TCGA、GTEx、SangerBox和TIMER 2.0数据库等生物信息学方法分析HJURP在各类癌症中的表达水平及其与预后、临床分期和免疫细胞浸润的关联。利用LinkedOmics数据库分析肾透明细胞癌（KIRC）中HJURP的相关基因及其潜在功能。通过免疫组织化学分析、Western blotting和qRT-PCR实验验证HJURP在KIRC中的表达，并设计靶向HJURP的小干扰RNA，评估其对KIRC细胞增殖、迁移能力的影响。结果: HJURP在包含KIRC的26种肿瘤组织中表达升高（P<0.05），且与包括KIRC的5种肿瘤患者的预后呈负相关（P<0.05）。HJURP的表达水平与肿瘤的临床分期及免疫细胞浸润密切相关。在KIRC中，HJURP表达升高（P<0.0001），且与TNM分期（P<0.05）、Stage分期（P<0.01）及免疫细胞浸润呈正相关。基因本体论功能分析结果显示：HJURP在生物学过程中主要富集于生物调节和代谢过程等；在细胞组分方面主要富集于细胞膜与细胞核等；在分子功能方面主要富集于蛋白质结合和离子结合等。组织和细胞水平实验显示，HJURP在KIRC中高表达（P<0.001），且沉默HJURP抑制KIRC细胞的增殖与迁移（P<0.01）。结论: HJURP可作为KIRC预后和免疫治疗的预测因子，并在KIRC细胞的恶性行为中发挥促进作用。.
Keywords: Holliday junction-recognition protein; kidney renal clear cell carcinoma; migration; pan-cancer; proliferation.