Structural maintenance of chromosomes 2 is identified as an oncogene in bladder cancer in vitro and in vivo
Structural maintenance of chromosomes 2 is identified as an oncogene in bladder cancer in vitro and in vivo
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DOI：
10.4149/neo_2020_190510n419
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发表时间：
2020-01-01
期刊：
影响因子：
3
通讯作者：
Sun, G. L.
中科院分区：
文献类型：
--
作者：
Han, Y. H.;Wan, Y.;Sun, G. L.
我们最近的研究发现牛磺酸上调基因 1 (TUG1) 可促进膀胱癌细胞生长。在这项研究中，使用 TUG1 耗尽的膀胱癌细胞来鉴定膀胱癌的有效参与者。人类基因表达阵列用于 TUG1 耗尽的膀胱癌细胞的转录组分析。通过MTT测定分析细胞增殖。通过流式细胞术分析细胞凋亡和细胞周期。采用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物形成测定。免疫组织化学染色用于测试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，失调的基因在细胞周期或癌症通路中大量富集。 TUG1 敲除后，2 号染色体 (SMC2) 的结构维持受到抑制。 TUG1 或 SMC2 的缺失导致膀胱癌细胞 G2/M 期停滞。 SMC2耗竭抑制膀胱癌细胞增殖，促进细胞凋亡，减少集落形成，并减少异种移植裸鼠中的肿瘤生长。 SMC2 的过度表达恢复了 TUG1 耗尽的细胞的生长。 SMC2在人膀胱癌组织中的表达水平高于配对的正常组织。我们的数据表明 SMC2 是膀胱癌的癌基因，消除 SMC2 可能对膀胱癌具有潜在的治疗意义。
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.