Background:
Bladder cancer is one of the most common
malignancies in urologic system. The
glucocorticoid-inducible
kinase 2 (SGK2) expression and function were largely unknown in
cancers. Current study was aimed to investigate the role of SGK2 in
bladder cancer and its potential mechanisms. Methods: SGK2 expression was quantified by western blot (WB) in multiple
bladder cancer cell lines (T24, 5637, J82 and UMUC3) compared with normal urothelial cell line (SVHUC). SGK2 knocking down and overexpression model were established by lentivirus transfection. MTT, colony formation, wound healing and transwell assay were used to assess the
tumor cell proliferation, migration and invasion abilities, respectively. In addition, molecular function analysis was performed using FunRich software V3. Immunoprecipitation (IP) assay was applied to investigate the interaction between SGK2 and β-
catenin at
protein level. TCGA database was retrieved to verify the association between these genes and clinical
tumor stage as well as prognosis among
bladder cancer patients. Results: SGK2 expression was significantly upregulated in multiple
bladder cancer cell lines compared with SVHUC at
protein level. Cell proliferation, migration and invasion abilities were significantly decreased after knocking down SGK2 in J82 and UMUC3 cell lines. Inversely, cell aggressive phenotypes were significantly increased after overexpressing SGK2 in T24 cell line. Furthermore, functional analyses of SGK2 based on TCGA database showed that SGK2 related genes were involved in receptor activity,
ATP binding, DNA repair
protein, trans-membrane receptor activity and
lipid binding. In addition,
protein interaction analysis identified c-Myc was significantly enriched in SGK2 positively associated genes. The prediction was validated by WB and IP assay that SGK2 could directly bind with β-
catenin at
protein level to regulate their downstream gene c-Myc expression in
bladder cancer to influence
tumor progression. And clinical data generated from TCGA database also identified these downstream genes were significantly associated with
tumor stage and survival status of
bladder cancer patients. Conclusion: Taken together, our findings suggest SGK2 promotes
bladder cancer progression via mediating β-
catenin/c-Myc signaling pathway, which may serve as a potential therapeutic target for
bladder cancer patients.