EPDR1 expression associates with PI3K/Akt activation and promotes aggressive phenotypes in bladder urothelial carcinoma

The ependymin-related protein gene (EPDR1) encodes a protein similar to ependymin and is widely expressed across human tissues, where it participates in several pathophysiological processes. Our previous work demonstrated that EPDR1 expression strongly correlates with tumor grade and metastasis in patients with bladder carcinoma, suggesting a potential role in bladder cancer (BLCA) development and progression. The present study investigated the biological functions of EPDR1 in bladder urothelial carcinoma and its possible mechanistic links to the PI3K/Akt pathway. We performed a series of experiments, including cell line establishment and grouping, quantitative real-time PCR (RT-qPCR), CCK-8 assays, colony formation assays, Transwell assays, Western blotting, electron microscopy, hematoxylin and eosin staining, immunohistochemistry, and animal studies. All data were analyzed using SPSS 20.0. EPDR1 significantly enhanced the proliferation, migration, and invasion of BLCA cells. Overexpression of EPDR1 increased the levels of phosphorylated PI3K and Akt, indicating activation of the PI3K/Akt signaling pathway. Pharmacologic inhibition of PI3K reduced the effects of EPDR1 overexpression and limited cell activity. In animal models, EPDR1 overexpression led to larger tumor volumes and faster tumor growth in nude mice, whereas EPDR1 knockdown resulted in smaller tumors with slower growth rates. EPDR1 is associated with aggressive tumor phenotypes in BLCA and correlates with activation of the PI3K/Akt signaling pathway. It may represent a potential therapeutic target and prognostic biomarker for patients with BLCA. However, further studies are needed to identify additional mechanisms by which EPDR1 may contribute to BLCA development and progression.