Deciphering the tumor-suppressive role of RBMS3 in lung adenocarcinoma through genomic insights into prognosis and mechanisms

作者：Li Lv, Telun Zhong, Zhenkun Li, Wenhui Zhang, Yi Zhang, Ying Liang, Rongqing Li, Mingxia Ding, Jie Lin · 发表于：Scientific Reports · 年份：2025 · DOI：10.1038/s41598-025-95432-w · 被引用次数：4 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、Cancer-related molecular mechanisms research

Lung adenocarcinoma (LUAD) is a leading cause of cancer-related mortality, underscoring the urgent need for novel biomarkers and therapeutic targets. Through transcriptomic analysis of 4456 genes in TCGA-LUAD cohorts, we identified RBMS3 as a significantly downregulated tumor suppressor (log 2 fold change = −1.82, adjusted P = 3.2 × 10⁻ 5 ). Clinically, elevated RBMS3 expression was independently associated with improved overall survival (HR = 0.766, 95% CI 0.602–0.973, P = 0.029), validated by Kaplan–Meier analysis (Log-rank P = 0.027). Functionally, RBMS3 overexpression in A549 and PC-9 LUAD cells suppressed invasion (66.53% and 52.46% reduction, respectively; P < 0.01) and induced apoptosis (total apoptosis increased by 6.53% and 8.57%; P < 0.05). Cell cycle analysis revealed accelerated G1-to-S phase transition, with G1-phase proportions decreasing from 44.6 to 36.87% in A549 ( P < 0.01) and from 49.83 to 37.13% in PC-9 ( P < 0.01). TIMER-based correlation analysis demonstrated a positive association between RBMS3 expression and immune cell infiltration, with the regression line indicating significant correlations for B cells (cor = 0.16, P = 4.25 × 10⁻ 4 ), CD8 + T cells (cor = 0.214, P = 1.86 × 10⁻⁶), CD4 + T cells (cor = 0.24, P = 8.99 × 10⁻⁸), macrophages (cor = 0.341, P = 1.07 × 10⁻ 14 ), neutrophils (cor = 0.277, P = 5.71 × 10⁻ 10 ), and dendritic cells (cor = 0.369, P = 3.70 × 10⁻ 17 ). These findings underscore RBMS3’s dual role in LUAD as a tumor suppressor and i...