POLR3G promotes EMT via PI3K/AKT signaling pathway in bladder cancer

• DOI: 10.1096/fj.202301095r
• Publication Date: 2023-11-07T13:55:16Z
• Authors: Hualin Chen; Lin Ma; Wenjie Yang; Yingjie Li; Zhigang Ji
• Keywords: Phosphatidylinositol 3-Kinases; Epithelial-Mesenchymal Transition; Urinary Bladder Neoplasms; Cell Movement; Cell Line, Tumor; Humans; RNA Polymerase III; Proto-Oncogene Proteins c-akt; 3. Good health; Cell Proliferation; Signal Transduction

AbstractRNA Polymerase III Subunit G (POLR3G) promotes tumorigenesis, metastasis, cancer stemness, and chemoresistance of breast cancer and lung cancer; however, its biological function in bladder cancer (BLCA) remains unclear. Through bioinformatic analyses, we found that POLR3G expression was significantly elevated in BLCA tumor tissues and was associated with decreased survival. Multivariate Cox analysis indicated that POLR3G could serve as an independent prognostic risk factor. Our functional investigations revealed that POLR3G deficiency resulted in reduced migration and invasion of BLCA cells both in vitro and in vivo. Additionally, the expressions of EMT‐related mesenchymal markers were also downregulated in POLR3G knockdown cells. Mechanistically, we showed that POLR3G could activate the PI3K/AKT signaling pathway. Inhibition of this pathway with LY294002 reduced the enhanced migration and invasion of BLCA cells induced by POLR3G overexpression, whereas the activation of this pathway using 740Y‐P restored the abilities that were inhibited by POLR3G knockdown. Taken together, our findings suggested that POLR3G is a prognostic predictor for BLCA and promotes EMT of BLCA through activation of the PI3K/AKT signaling pathway.