胃癌(GC)是全球主要的健康问题,预后不佳。HNRNPU是一种参与前mRNA包装的多功能蛋白,选择性拼接调节,和染色质重塑。其在GC中的潜在作用尚不清楚。在这项研究中,通过TCGA数据分析HNRNPU的表达特征,GEO数据,然后使用组织标本通过实时定量PCR和免疫组织化学进一步鉴定。从浅表性胃炎,萎缩性胃炎,增生为GC,HNRNPU蛋白的原位表达逐渐增加,以及诊断GC及其癌前病变的AUC,GC分别为0.911、0.847。整合HNRNPU表达的列线图,淋巴结转移和其他预后指标显示预测生存风险的AUC为0.785。敲除HNRNPU显著抑制GC细胞增殖,迁移,侵袭和促进细胞凋亡。此外,RNA-seq分析显示HNRNPU可影响GC细胞的可变剪接事件,功能富集分析显示HNRNPU可能通过可变剪接调控在GC进程中发挥恶性生物学功能。总之,HNRNPU的表达增加与GC的发展显着相关,在诊断和预测GC的预后风险方面具有良好的性能。功能上,HNRNPU可能通过调节可变剪接在GC中发挥致癌作用。
Gastric cancer (GC) is a major global health concern with poor outcomes. Heterogeneous nuclear ribonucleoprotein U (
HNRNPU) is a multifunctional protein that participates in pre-mRNA packaging, alternative splicing regulation, and chromatin remodeling. Its potential role in GC remains unclear. In this study, the expression characteristics of
HNRNPU were analyzed by The Cancer Genome Atlas data, Gene Expression Omnibus data, and then further identified by real-time quantitative PCR and immunohistochemistry using tissue specimens. From superficial gastritis, atrophic gastritis, and hyperplasia to GC, the in situ expression of
HNRNPU protein gradually increased, and the areas under the curve for diagnosis of GC and its precancerous lesions were 0.911 and 0.847, respectively. A nomogram integrating HNRNPU expression, lymph node metastasis, and other prognostic indicators exhibited an area under the curve of 0.785 for predicting survival risk. Knockdown of HNRNPU significantly inhibited GC cell proliferation, migration, and invasion and promoted apoptosis in vitro. In addition, RNA-sequencing analysis showed that
HNRNPU could affect alternative splicing events in GC cells, with functional enrichment analysis revealing that HNRNPU may exert malignant biological function in GC progression through alternative splicing regulation. In summary, the increased expression of HNRNPU was significantly associated with the development of GC, with a good performance in diagnosing and predicting the prognostic risk of GC. Functionally,
HNRNPU may play an oncogenic role in GC by regulating alternative splicing.