MiR-186 suppresses the growth and metastasis of bladder cancer by targeting NSBP1
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RESEARCH
Open Access
MiR-186 suppresses the growth and metastasis of bladder cancer by targeting NSBP1 Kun Yao, Leye He, Yu Gan, Qing Zeng, Yingbo Dai and Jing Tan*
Abstract Background: Increasing evidence has shown that microRNAs function as oncogenes or tumor suppressors in human malignancies, but the roles of miR-186 in human bladder cancer (BC) is still unclear. Methods: First, quantitative real-time PCR (qRT-PCR) was performed to detect miR-186 expression in bladder cancer tissues and cell lines. Then, Bioinformatics analysis, combined with luciferase reporter assay demonstrated the target gene of miR-186. Finally, the roles of miR-186 in regulation of tumor proliferation and invasion were further investigated. Results: Here, our study showed miR-186 was down-regulated in bladder cancer tissues and cell lines. Luciferase reporter assay showed that miR-186 targets NSBP1 3′-untranslated region (UTR) directly and suppresses NSBP1 (HMGN5) expression in human bladder cancer cells. NSBP1 siRNA- and miR-186-mediated NSBP1 knock-down experiments revealed that miR-186 suppresses cell proliferation and invasion through suppression of NSBP1 expression. Expression analysis of a set of epithelial-mesenchymal transition (EMT) markers showed that NSBP1 involves miR-186 suppressed EMT which reducing the expression of mesenchymal markers (vimentin and N-cadherin) and inducing the expression of epithelial marker (E-cadherin). Conclusions: Our data first time identified miR-186 as the upstream regulator of NSBP1 and also suggest miR-186suppressed NSBP1 as a novel therapeutic approach for bladder cancer.
Background Bladder cancer is the most common malignancy involving the urinary system with more than 350,000 new cases diagnosed globally each year [1, 2]. Bladder cancer is the fourth most common cancer in males and ninth most common in females, and is by far the most frequent urological malignancy in China [3]. Despite significant advances in accurate and effective diagnostic and therapeutic methods, bladder cancer remains a highly prevalent and lethal malignancy [4]. Therefore, it is urgent for novel treatment strategies based on new molecular networks to improve the poor prognosis in patients with bladder cancer. High mobility group N (HMGN) proteins are a family of ubiquitous nuclear proteins which modify the structure of chromatin to attain a conformation that * Correspondence: [email protected] Department of Urology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha 410013 Hunan, China
facilitates and enhances transcription, histone modifications, replication and repair [5, 6]. NSBP1 (Nucleosomal Binding Protein 1), also named HMGN5, is a new member of the HMGN protein family, is reported to bind to the nucleosomes via nucleosomal binding domain (NBD), unfold chromatin, and modulate gene transcription [7]. Accumulating studies showed that NSBP1 was abundantly expressed in various types of cancer, including gliomas [8], clear cell renal cell carcinoma [9] and prostate cancer [10]. Re
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