Zhengliang Li, Xiaojing Liu, Jundong Wang, Jiaxi Wang, Guoxiang Jiang, Haizhou Yu
As an oncogenic circRNA, hsa_circ_0001839 is critically implicated in gastric cancer progression and unfavorable patient outcomes, underscoring its dual application as a promising prognostic biomarker and a potential therapeutic intervention target.
BACKGROUND AND STUDY AIMS: Circular RNAs (circRNAs) are characterized by their covalently closed-loop configuration. They are increasingly being recognized as key modulators of tumorigenesis and cancer progression. Studies have revealed aberrant hsa_circ_0001839 expression in various cancer types. However, its effect and underlying mechanisms in gastric cancer (GC) remain unknown. Therefore, we systematically investigated the clinical importance of hsa_circ_0001839 in gastric cancer and its molecular mechanisms in disease progression.
PATIENTS AND METHODS: Paired tumor specimens and histologically normal adjacent tissues were collected from 117 patients with GC who underwent curative surgery. RT-qPCR was performed to measure hsa_circ_0001839 expression in clinical samples and cell lines. Kaplan-Meier survival curves and Cox proportional hazards models were used to evaluate the prognostic relevance of this circRNA. Lastly, cell transfection, CCK-8, Transwell invasion, and dual-luciferase reporter assays were performed to validate the functional effects on GC cells and regulatory interactions with target genes.
RESULTS: Compared with matched non-tumor tissues, hsa_circ_0001839 expression was markedly increased in gastric cancer tissues. High hsa_circ_0001839 expression significantly correlated with larger tumor dimensions, deeper invasion depth, advanced TNM stage, and the presence of lymph node metastasis. Multivariate Cox analysis revealed that high hsa_circ_0001839 expression is an independent predictor of poor prognosis. Functionally, hsa_circ_0001839 knockdown effectively suppressed the malignant phenotypes of GC cells, significantly decreasing their proliferative, migratory, and invasive abilities. Mechanistically, hsa_circ_0001839 directly binds to the 3'-untranslated region of miR-634, thereby repressing its function.
CONCLUSION: As an oncogenic circRNA, hsa_circ_0001839 is critically implicated in gastric cancer progression and unfavorable patient outcomes, underscoring its dual application as a promising prognostic biomarker and a potential therapeutic intervention target.