UBC9 coordinates inflammation affecting development of bladder cancer.
UBC9 coordinates inflammation affecting development of bladder cancer.
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UBC9 协调影响膀胱癌发展的炎症。
DOI：
10.1038/s41598-020-77623-9
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发表时间：
2020-11-26
影响因子：
4.6
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Huang X;Tao Y;Gao J;Zhou X;Tang S;Deng C;Lai Z;Lin X;Wang Q;Li T
SUMO修饰的失调与癌发生有关。UBC 9是SUMO化中唯一的结合酶，在维持体内平衡和抑制应激反应中起着关键作用。然而，UBC 9在膀胱癌中的临床意义和功能尚不清楚。本研究采用免疫组织化学方法检测UBC 9的表达。进行UBC 9敲低和SUMO抑制，然后进行增殖、迁移和细胞周期测定。RNA测序和生物信息学分析用于确定UBC 9的潜在机制。细胞因子膜抗体芯片检测细胞因子的表达。采用质谱TOF技术（CyTOF）探讨膀胱癌干细胞样细胞群与UBC 9表达的关系。我们的研究结果表明，UBC 9在膀胱癌中发挥双重作用。UBC 9在膀胱癌中表达上调，但与TNM分期和分级呈负相关。UBC 9基因的敲除可显著激活炎症基因的表达，从而抑制细胞增殖，诱导细胞凋亡。IL 6是UBC 9调控网络的枢纽基因。在敲低UBC 9后显著上调的IL 6激活了CD 44的表达，这是癌症干细胞的显著标志物。因此，我们的研究结果揭示了UBC 9在膀胱癌炎症信号传导调节中的重要且先前未描述的作用。膀胱癌细胞中的UBC 9是维持高sumoylation水平和减轻对细胞存活的应激相关炎症威胁所必需的。缺乏UBC 9有助于炎症激活，上皮-间质转化和干细胞样群体形成，导致癌症进展。
Dysregulation of SUMO modification is linked to carcinogenesis. UBC9 is the sole conjugating enzyme in sumoylation and plays a pivotal role in maintaining homeostasis and restraining stress reactions. However, the clinical significance and function of UBC9 in bladder cancer remain unclear. In this study, immunohistochemistry was used to determine the expression of UBC9. UBC9 knock-down and SUMO inhibition were conducted followed by proliferation, migration, and cell cycle assays. RNA sequencing and bioinformatic analysis were used to identify potential mechanisms of UBC9. Cytokine membrane antibody array was used to detect the expression of cytokine. The mass cytometry TOF (CyTOF) was used to explore the association between bladder cancer stem cell-like population and UBC9 expression. Our results showed that UBC9 played a dual role in bladder cancer. UBC9 was up-regulated in bladder cancer, but was negatively correlated with TNM stage and grade. Knocking-down of UBC9 resulted in dramatic activation of inflammatory gene expression, which might cause inhibition of cell proliferation and inducing cell apoptosis. IL6 was the hub gene in UBC9 regulatory network. Markedly up-regulated IL6 after knocking-down of UBC9 activated the expression of CD44, which was a prominent marker of cancer stem cells. Thus, our results revealed an important and previously undescribed role for UBC9 in modulation of inflammatory signaling of bladder cancer. UBC9 in bladder cancer cells is required to maintain high sumoylation levels and alleviate stress-related inflammation threats to cell survival. Lacking UBC9 contributes to inflammation activation, epithelial–mesenchymal transition and stem cell-like population formation, leading to cancer progression.
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影响因子：
4.8
作者：
Ren JL;Pan JS;Lu YP;Sun P;Han J
通讯作者：
Han J
影响因子：
--
作者：
Li Y;Lin K;Yang Z;Han N;Quan X;Guo X;Li C
通讯作者：
Li C
肝癌的发生需要通过 CD44 增强的生长因子信号传导抑制 p53
影响因子：
50.3
作者：
Dhar D;Antonucci L;Nakagawa H;Kim JY;Glitzner E;Caruso S;Shalapour S;Yang L;Valasek MA;Lee S;Minnich K;Seki E;Tuckermann J;Sibilia M;Zucman-Rossi J;Karin M
通讯作者：
Karin M
DOI：
10.1016/j.biocel.2016.09.009
发表时间：
2016-12-01
影响因子：
4
作者：
Morath, I.;Hartmann, T. N.;Orian-Rousseau, V.
通讯作者：
Orian-Rousseau, V.
影响因子：
4.3
作者：
Gervois, Pascal;Ratajczak, Jessica;Lambrichts, Ivo
通讯作者：
Lambrichts, Ivo