Persistent activation of NF-κB signaling is closely related to chronic inflammation and tumorgenesis. Commonly, NF-κB signaling is tightly controlled by multiple feedback loops and regulators, such as the deubiquitinases (DUBs). However, in cancer cells, NF-κB may override these feedbacks through special pathways and lead to the sustained activation. In the present study, we demonstrate that in transitional cell carcinoma (TCC) of bladder, miR-130b plays an oncogenesis role, it enhanced proliferation, invasion and migration of TCC cell, and was highly correlated with tumor progression. On the other hand, NF-κB directly regulated the transcription of miR-130b by binding with its promoter region. Importantly, we verify that, through deceasing the expression of Cylindromatosis (CYLD), a K63-specific DUB and endogenous blocker of NF-κB signaling, miR-130b can in return sustain the persistent activation of NF-κB, which may promote the malignant progression of TCC. Thus, the present study uncovers a potential signaling transduction in which NF-κB is continuously activated, and may provide a novel therapeutic approach for the clinical management of TCC.
Oncotarget. 2016 Jul 06 [Epub ahead of print]
Xiaolu Cui, Chuize Kong, Yuyan Zhu, Yu Zeng, Zhe Zhang, Xiankui Liu, Bo Zhan, Chiyuan Piao, Zhenming Jiang
Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China., Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China., Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China., Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China., Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China., Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China., Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China., Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China., Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.