Department of Clinical Medicine, Tibet University Medical College, Lhasa, China.
Department of Geriatric Medicine and Neurology, West China School of Public Health and West China Forth Hospital, Sichuan University, Chengdu, China.
Neoplasma. 2020 Mar;67(2):364-370. doi: 10.4149/neo_2020_190510N419. Epub 2020 Jan 27.
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.
牛磺酸上调基因 1（TUG1）在我们最近的研究中被发现可促进膀胱癌细胞生长。在这项研究中，我们使用 TUG1 耗尽的膀胱癌细胞来鉴定膀胱癌中的潜在关键因子。采用人类基因表达谱芯片对 TUG1 耗尽的膀胱癌细胞进行转录组谱分析。通过 MTT 检测分析细胞增殖。通过流式细胞术分析细胞凋亡和细胞周期。通过集落形成实验观察集落形成率的变化。在裸鼠中进行异种移植形成实验。免疫组织化学染色用于检测膀胱癌患者组织中的基因表达水平。我们发现，在 TUG1 耗尽的膀胱癌细胞中，失调基因在细胞周期或癌症途径中强烈富集。TUG1 敲低后结构维持染色体 2（SMC2）受到抑制。TUG1 或 SMC2 的耗竭导致膀胱癌细胞停滞在 G2/M 期。SMC2 耗竭抑制膀胱癌细胞增殖，促进细胞凋亡，减少集落形成，并减少裸鼠异种移植肿瘤的生长。SMC2 的过表达恢复了 TUG1 耗尽细胞的生长。SMC2 的表达水平在人类膀胱癌组织中高于配对的正常组织。我们的数据表明，SMC2 是膀胱癌中的一种癌基因，SMC2 的耗竭可能在膀胱癌的治疗中有潜在的治疗意义。
