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首页> 外文期刊>British Journal of Cancer >MicroRNA-126 inhibits invasion in bladder cancer via regulation of ADAM9
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MicroRNA-126 inhibits invasion in bladder cancer via regulation of ADAM9

机译：MicroRNA-126通过调节ADAM9抑制膀胱癌的侵袭

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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.
机译：背景：miRNA失调通常在人类恶性肿瘤中观察到，在恶性肿瘤中它们充当肿瘤抑制因子或致癌基因。尽管有几种miRNA与膀胱癌相关联，但对于导致膀胱癌从非肌肉浸润（NMI）到肌肉浸润（MI）疾病发展的miRNA知之甚少。方法：我们首先分析了miRNA和mRNA的表达在一组尿路上皮癌中，并进一步表征了miR-126在侵袭中的作用，因为它是MI和NMI肿瘤之间最下调的miRNA。结果：我们发现miR-126水平的恢复减弱了膀胱癌的浸润潜力。细胞。从机制上讲，我们通过miR-126靶向ADAM9的能力确定了其在侵袭中的作用。值得注意的是，观察到miR-126与ADAM9表达之间存在显着的逆相关性，其中ADAM9在MI膀胱癌细胞中被上调。虽然敲低ADAM9会减弱低miR-126水平的细胞的侵袭性，但ADAM9的实验性上调概括了侵袭性表型。此外，通过免疫组织化学评估的ADAM9表达与尿路上皮癌患者的不良预后显着相关。结论：在这项研究中，我们描述了miR-126在膀胱癌进展中的作用，将miR-126和ADAM9鉴定为疾病侵袭性的潜在临床生物标志物。

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