Wang Zhongyu, Shang Jun, Li Zhiqin, Li Huanhuan, Zhang Chufan, He Kai, Li Shikang, Ju Wen
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Front Oncol. 2020 Dec 3;10:536072. doi: 10.3389/fonc.2020.536072. eCollection 2020.
PIK3CA is a key component of phosphatidylinositol 3-kinase (PI3K) pathway that its involvement in tumorigenesis has been revealed by previous research. However, its functions and potential mechanisms in bladder cancer are still largely undiscovered. Tissue microarray (TMA) with 66 bladder cancer patients was surveyed immunohistochemistry to evaluate the level of PIK3CA and CUX1 and we found upregulation of PIK3CA in bladder cancer tissue and patients with higher level of PIK3CA presented with poorer prognosis. Overly expressed PIK3CA promoted growth, migration, invasion, and metastasis of bladder cancer cells and knockdown of PIK3CA had the opposite effect. Gain-of-function and loss-of-function studies showed that expression was facilitated by CUX1, leading to activation of epithelial-mesenchymal transition (EMT), accompanied by upregulated expression of Snail, β-catenin, Vimentin and downregulated expression of E-cadherin in the bladder cancer cell lines. Besides, over-expressed CUX1 could restore the expression of downregulated Snail, β-catenin, Vimentin and E-cadherin which was induced by PIK3CA knockdown. These results revealed that overexpression in bladder cancer was regulated by the transcription factor CUX1, and exerted its biological effects by activating EMT.
PIK3CA是磷脂酰肌醇3激酶（PI3K）信号通路的关键组成部分，先前的研究已揭示其参与肿瘤发生过程。然而，其在膀胱癌中的功能及潜在机制仍大多未知。本研究采用免疫组化方法对66例膀胱癌患者的组织芯片（TMA）进行检测，以评估PIK3CA和CUX1的表达水平。结果发现，PIK3CA在膀胱癌组织中上调，PIK3CA水平较高的患者预后较差。过表达的PIK3CA促进膀胱癌细胞的生长、迁移、侵袭和转移，而敲低PIK3CA则产生相反的效果。功能获得和功能丧失研究表明，CUX1促进PIK3CA的表达，导致上皮-间质转化（EMT）激活，伴随膀胱癌细胞系中Snail、β-连环蛋白、波形蛋白表达上调，E-钙黏蛋白表达下调。此外，过表达的CUX1可恢复因PIK3CA敲低而导致的Snail、β-连环蛋白、波形蛋白和E-钙黏蛋白表达下调。这些结果表明，膀胱癌中PIK3CA的过表达受转录因子CUX1调控，并通过激活EMT发挥其生物学作用。
