Alternative Splicing Factor HNRNPU as a Promising Biomarker for Gastric Cancer Risk and Prognosis with Tumor-Promoting Properties

Gastric cancer (GC) is a major global health concern with poor outcomes. 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 TCGA data, GEO data, then further identified by real-time quantitative PCR and immunohistochemistry using tissue specimens. From superficial gastritis, atrophic gastritis, hyperplasia to GC, the in situ expression of HNRNPU protein gradually increased, and the AUCs for diagnosis of GC and its precancerous lesions, GC were 0.911, 0.847, respectively. A nomogram integrating HNRNPU expression, lymph node metastasis and other prognostic indicators exhibited an AUC of 0.785 for predicting survival risk. Knockdown of HNRNPU significantly inhibited GC cell proliferation, migration, invasion and promoted apoptosis in vitro. Additionally, RNA-seq 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.