title: miR-130b, an onco-miRNA in bladder cancer, is directly regulated by NF-κB and sustains NF-κB activation by decreasing Cylindromatosis expression.
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.
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Chuize
authors.initials: C
authors.lastname: Kong
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Xiankui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhan
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Chiyuan
authors.initials: C
authors.lastname: Piao
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Jiang
mesh_terms: D000368:Aged; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D000074749:Deubiquitinating Enzyme CYLD / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009857:Oncogenes; D015398:Signal Transduction / Q000235:genetics*; D015854:Up-Regulation; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D023041:Xenograft Model Antitumor Assays
chemical_list: C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD
keywords: CYLD; NF-κB; bladder transitional cell carcinoma; miR-130b