As a New Tumor Suppressor Gene, PID1 Activates the AMPK-mTOR Signal to Inhibit the Progression of Bladder Cancer.

Purpose: Bladder cancer is one of the ten most common cancers in the world, with a high incidence rate and mortality, and therefore a major burden on the global health care system. PID1 (Phosphotyrosine Interaction Domain 1) functions as an intracellular receptor protein for LRP1. The purpose of this study was to explore the role of PID1 in bladder cancer.

Methods: RNA-seq data analysis was conducted on 404 BLCA specimens and 28 normal specimens to identify differentially expressed genes. The findings indicated a strong correlation between PID1 expression levels and bladder cancer. We constructed a bladder cancer cell line stably overexpressing PID1 and assessed its impact on cell proliferation and migration. Additionally, We used RT-112 cells to induce tumor formation in nude mice to study the function of the gene in vivo.

Results: PID1 expression was notably low in bladder cancer tissues. Compared to SV-HUC-1, RT-112, and SCaBER bladder cells exhibited significantly reduced PID1 expression. Overexpressing PID1 in cells led to the promotion of apoptosis in bladder cancer cells and suppressed cell proliferation and metastasis. In vivo, the overexpression of PID1 demonstrated a significant inhibitory effect on bladder cancer. Furthermore, it was capable of activating the AMPK-mTOR signaling pathway, thereby inhibiting tumor progression.

Conclusion: PID1 exhibits a potent inhibitory effect on bladder cancer and activates the AMPK-mTOR signaling pathway to hinder tumor growth.