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Oncotarget. 2016 Jul 26;7(30):48547-48561. doi: 10.18632/oncotarget.10423.

miR-130b, an onco-miRNA in bladder cancer, is directly regulated by NF-κB and sustains NF-κB activation by decreasing Cylindromatosis expression.

Author information

1
Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.

Abstract

Persistent activation of NF-κB signaling is closely related to chronic inflammation and tumorigenesis. 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.

KEYWORDS:

CYLD; NF-κB; bladder transitional cell carcinoma; miR-130b

PMID:
27391066
PMCID:
PMC5217037
DOI:
10.18632/oncotarget.10423
[Indexed for MEDLINE]
Free PMC Article

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