MicroRNA-126 inhibits invasion in bladder cancer via regulation of ADAM9.
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.
Department of Pathology and Cell Biology, Columbia University, 1130 St Nicholas Avenue, New York, NY 10032, USA.
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AY
Jia
Department of Pathology, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY 10029, USA.
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Castillo-Martin
Department of Pathology, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY 10029, USA.
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DM
Bonal
Proteomics Laboratory 3, CIC Biogune, Parque Tecnológico de Vizcaya, Derio, Vizcaya 48160, Spain.
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Sánchez-Carbayo
Department of Pathology and Cell Biology, Columbia University, 1130 St Nicholas Avenue, New York, NY 10032, USA.
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JM
Silva
1] Department of Pathology, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY 10029, USA [2] Department of Urology, Columbia University, 1130 St Nicholas Avenue, New York, NY 10032, USA.
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Cordon-Cardo
D051722:ADAM Proteins / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D034622:RNA Interference; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*
D014408:Biomarkers, Tumor; C527111:MIRN126 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D051722:ADAM Proteins; C098339:ADAM9 protein, human