Non-Coding RNA Hubs in Bladder Cancer Highlight Potential Liquid Biopsy Candidates

Bladder cancer (BLCA) is a highly recurrent and heterogeneous malignancy, with current diagnostics such as cystoscopy and urine cytology being invasive or insufficiently sensitive. Non-coding RNAs (ncRNAs), particularly long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play key roles in tumor biology and hold promise as liquid biopsy biomarkers; however, most studies focus on individual ncRNAs, overlooking their coordinated regulation through competing endogenous RNA (ceRNA) networks. Here, we performed integrative bioinformatics analysis of TCGA-BLCA transcriptomes, identifying 1,248 mRNAs, 163 lncRNAs, and 72 miRNAs as differentially expressed. Using network modeling, correlation filtering, and functional enrichment, we reconstructed lncRNA–miRNA–mRNA ceRNA triplets, revealing oncogenic modules (e.g., LINC00460–miR-21–PTEN/PDCD4; LINC02884–miR-130b–RUNX3/PTEN) converging on PI3K/AKT, Wnt, and TGF-β pathways to promote proliferation and EMT, and tumor suppressor modules (e.g., ADAMTS9-AS1–miR-210–HIF3A/E2F3; CARMN–miR-145–SOX2/OCT4) reinforcing apoptosis, angiogenesis inhibition, and stemness suppression. Centrality analyses identified LINC00460, HAND2-AS1, ADAMTS9-AS1, and CARMN as master hubs, with recurrent mRNA targets including PTEN, VEGFA, and ZEB1 acting as network bottlenecks. By mapping redundant and convergent ceRNA architectures, this study highlights hub lncRNAs as system-level regulators rather than isolated candidates. These hubs represent strong candidates for liquid biopsy applications, enabling early detection, tumor subtype stratification, and real-time therapy monitoring. Overall, our integrative approach bridges molecular insight with translational relevance, providing a blueprint for developing ncRNA-based diagnostic and prognostic tools in bladder cancer.