Acta histochemica · 2024
Exploring the oncogenic role of RGS19 in bladder cancer progression and prognosis.
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Yan Lei, Luo Guangyue, Han Chengxiang, Meng Jialin, Liang Chaozhao
Аннотация
This study investigates the role of autophagy-related genes (ARGs) in bladder cancer (BLCA), focusing on the regulator of G protein signaling 19 (RGS19). Using data from The Cancer Genome Atlas (TCGA) and the Human Autophagy Database (HADb), we identified RGS19 as significantly upregulated and linked to poor prognosis in BLCA. Kaplan-Meier survival analysis confirmed its association with increased mortality and. In vitro, RGS19 knockdown in BLCA cell lines inhibited proliferation, migration, and invasion, while inducing apoptosis and autophagy. Transmission electron microscopy showed autophagic structures in RGS19-silenced cells. In vivo, a xenograft mouse model demonstrated reduced tumor growth with RGS19 knockdown. Immunohistochemical (IHC) analysis revealed decreased Ki67 and increased autophagy markers in tumors with reduced RGS19. Pathway analysis suggested RGS19 acts through the cGMP-PKG signaling pathway, validated by altered expression of soluble guanylate cyclase (sGC), protein kinase G (PKG1), phosphodiesterase 5 A (PDE5A), vasodilator-stimulated phosphoprotein (VASP), and phosphorylated VASP (p-VASP) upon RGS19 knockdown. These results highlight RGS19 as a potential biomarker and therapeutic target in BLCA.