The Upregulation of LINC01048 Activates YAP1, Thereby Impacting the Biological Function and Extracellular Matrix of Bladder Cancer via the Wnt/-catenin Pathway

Background: LINC01048 is a recognized oncogene. LINC01048 regulates cellular functions through various mechanisms, affecting gene expression, activating cellular signaling pathways, and modulating the cellular functions. The primary aim of this research is to explore how LINC01048 influences the biological function of bladder cancer (BC) and the extracellular matrix (ECM), along with its regulatory role in the yes-related protein 1 (YAP1)/Wnt/beta-catenin pathway.Method: Data from The Cancer Genome Atlas (TCGA) data was utilized to acquire lncRNA expression and clinical information for bladder cancer (BC). Differential analysis compared normal and tumor groups, followed by survival analysis for the target lncRNA. Gene Set Enrichment Analysis (GSEA) identified regulatory pathways associated with LINC01048. Clinical samples were collected to measure LINC01048 expression in BC patients, and its correlation with clinical features was analyzed. In BC cell lines and normal bladder cells, LINC01048 mRNA expression was measured by Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR). Two groups of cells, with high and low LINC01048 expression, were transfected, and post-transfection levels were quantified. Cell proliferation, apoptosis, ECM receptor-related proteins (Collagen I, alpha-smooth muscle actin (alpha-SMA), Integrin alpha 6 (ITGA6), CD44), and pathway proteins (YAP1/Wnt/beta-catenin) were assessed using Cell Counting Kit-8 (CCK-8), clonogenic formation, flow cytometry, and Western blot. Stable cell lines with high or low LINC01048 expression were established and injected into nude mice to create a BC model. Changes in tumor volume and mass were monitored among different transfection groups. LINC01048 expression in tumor tissues and pathway protein levels were measured.Result: LINC01048 was significantly overexpressed in both BC tissues and cell lines, showing a strong association with the ECM receptor interaction pathway. Overexpression enhanced BC cell growth, increased ECM receptor interaction proteins, and elevated YAP1/Wnt/beta-catenin pathway proteins while decreasing apoptosis. si-LINC01048 transfection yielded opposite effects (p < 0.05). In a nude mouse BC model, overexpression led to significantly larger tumor volumes, higher expression of ECM receptor interaction proteins, and upregulation of YAP1/Wnt/beta-catenin pathway proteins compared to the control group. si-LINC01048 led to smaller BC volumes, reduced expression of ECM receptor interaction proteins, and downregulation of YAP1/Wnt/beta-catenin pathway proteins (p<0.05).Conclusion: In bladder cancer, LINC01048 promotes the expression of ECM receptor interaction proteins and cellular behaviors by activating the YAP1/Wnt/beta-catenin signaling pathway.