MicroRNA-126 inhibits invasion in bladder cancer via regulation of ADAM9

• Published in: British journal of cancer Vol. 110; no. 12; pp. 2945 - 2954
• Main Authors: Jia, A Y, Castillo-Martin, M, Bonal, D M, Sánchez-Carbayo, M, Silva, J M, Cordon-Cardo, C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.06.2014; Nature Publishing Group
• Subjects: 631/337/384/331; 631/67/589/1336; 631/80/84/2336; ADAM Proteins - genetics; Apoptosis - genetics; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Bladder cancer; Cancer Research; Cell Line, Tumor; Cell Proliferation; Drug Resistance; Epidemiology; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Medical sciences; Membrane Proteins - genetics; MicroRNAs - genetics; MicroRNAs - physiology; Molecular Diagnostics; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Invasiveness; Nephrology. Urinary tract diseases; Oncology; Prognosis; RNA Interference; Tumors; Tumors of the urinary system; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; Urinary tract. Prostate gland; microRNA; ADAM9; miR-126; invasion; bladder cancer; Urinary system disease; RNA interference; Micro RNA; Tumorous infiltration; Urinary tract disease; Malignant tumor; Metastasis; Bladder cancer; Invasion; Gene silencing; Regulation(control); Cancerology; Bladder disease; Inhibitor; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2014.245

Background: The miRNA deregulation is commonly observed in human malignancies, where they act as tumour suppressors or oncogenes. Despite the association of several miRNAs with bladder cancer, little is known about the miRNAs that contribute to bladder cancer progression from non-muscle invasive (NMI) to muscle-invasive (MI) disease. Methods: We first profiled the expression of miRNAs and mRNAs in a cohort of urothelial carcinomas and further characterised the role of miR-126 in invasion, as it emerged as the most downregulated miRNA between MI and NMI tumours. Results: We found that restoration of miR-126 levels attenuated the invasive potential of bladder cancer cells. Mechanistically, we identified the role of miR-126 in invasion through its ability to target ADAM9. Notably, a significant inverse correlation between miR-126 and ADAM9 expression was observed, where ADAM9 was upregulated in MI bladder cancer cells. While knockdown of ADAM9 attenuated the invasiveness of cells with low miR-126 levels, experimental upregulation of ADAM9 recapitulated the invasive phenotype. Furthermore, ADAM9 expression assessed by immunohistochemistry significantly correlated with poor prognosis in patients with urothelial carcinoma. Conclusions: In this study we describe the role of miR-126 in bladder cancer progression, identifying miR-126 and ADAM9 as potential clinical biomarkers of disease aggressiveness.