Structural maintenance of chromosomes 2 is identified as an oncogene in bladder cancer in vitro and in vivo

 Yong-Hua Han, Yang Wan, Hai Xiong, Gui-Li Sun

Abstract:

Taurine upregulated gene 1 (TUG1) has been found to promote bladder cancer cell growth in our recent research. In this study, TUG1-depleted bladder cancer cells were used to identify potent players in bladder cancer. Human gene expression arrays were used for transcriptome profiling of TUG1-depleted bladder cancer cells. Cell proliferation was analyzed by MTT assay. Cell apoptosis and cell cycle were analyzed by flow cytometry. Colony formation assay was used to observe the changes of colony formation rates. Xenograft formation assay was performed in nude mice. Immunohistochemical staining was used to test the gene expression levels in tissues from bladder cancer patients. We found that deregulated genes were strongly enriched in cell cycle or pathways in cancer in TUG1-depleted bladder cancer cells. Structural maintenance of chromosomes 2 (SMC2) was inhibited after TUG1 knockdown. The depletion of TUG1 or SMC2 led to G2/M phase arrest in bladder cancer cells. SMC2 depletion inhibited bladder cancer cell proliferation, promoted apoptosis, decreased colony formation, and reduced tumor growth in xenograft nude mice. Overexpression of SMC2 restored the growth of TUG1-depleted cells. The expression levels of SMC2 were higher in human bladder cancer tissues than that in paired normal tissues. Our data suggest that SMC2 is an oncogene in bladder cancer and depletion of SMC2 might have potential therapeutical significance in bladder cancer.