[Holliday junction-recognizing protein is a potential predictive and prognostic biomarker for kidney renal clear cell carcinoma].

Q3 Medicine

南方医科大学学报杂志 Pub Date : 2024-12-20 DOI:10.12122/j.issn.1673-4254.2024.12.10

Huahua Zhang, Qingyin Ta, Yun Feng, Jiming Han

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引用次数: 0

Abstract

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.

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[Holliday连接识别蛋白是肾透明细胞癌的潜在预测和预后生物标志物]。

目的：探讨Holliday交叉识别蛋白（HJURP）在肿瘤发生、进展和免疫治疗反应中的作用。方法：采用生物信息学方法，应用TCGA、GTEx、SangerBox、TIMER 2.0数据库，分析HJURP在各种肿瘤中的表达水平及其与预后、临床分期、免疫细胞浸润的关系。采用LinkedOmics数据库研究hjurp相关基因在肾透明细胞癌（KIRC）中的作用。采用免疫组织化学、Western blotting和qRT-PCR检测HJURP在KIRC细胞中的表达，并在培养的KIRC细胞中检测HJURP沉默对细胞增殖和迁移的影响。结果：HJURP在26例肿瘤中高表达，与KIRC等5例患者的生存结局呈负相关（PHJURP表达水平与肿瘤的临床分期和免疫细胞浸润密切相关）。在KIRC中，HJURP的表达显著升高（PPPHJURP主要在生物调控和代谢过程中富集）。关于细胞成分，HJURP主要定位于细胞膜和细胞核。在分子功能上，主要富集与蛋白质结合和离子结合有关的活性。HJURP在临床KIRC组织和KIRC细胞系中均高表达（PHJURP显著抑制细胞增殖和迁移能力）。结论：HJURP可能是KIRC预后和免疫治疗反应的一个指标，其高表达增强了KIRC细胞的恶性行为。

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