Elsevier

Neoplasia

Volume 15, Issue 2, February 2013, Pages 218-230, IN30-IN31
Neoplasia

MicroRNA-145 Targets the Metalloprotease ADAM17 and Is Suppressed in Renal Cell Carcinoma Patients1

https://doi.org/10.1593/neo.121222Get rights and content
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Abstract

A disintegrin and metalloproteinase 17 (ADAM17) is a metalloprotease that is overexpressed in many cancer types, including renal cancers. However, the regulatory mechanisms of ADAM17 in cancer development and progression are poorly understood. In the present work, we provide evidence using overexpression and inhibition of microRNA 145 (miR-145) that miR-145 negatively regulates ADAM17 expression. Furthermore, we show that ADAM17 negatively regulates miR-145 through tumor necrosis factor-α, resulting in a reciprocal negative feedback loop. In this study, the expression of ADAM17 and miR-145 correlated negatively in renal cancer tumor tissues and cell lines, suggesting an important regulatory mechanism. Additionally, we showed that the regulation of ADAM17 is partly involved in the effects of miR-145 on proliferation and migration, whereas no involvement in chemosensitivity was observed. Importantly, in the healthy kidney, miR-145 was detected in different cell types including tubular cells, which are considered the origin of renal cancer. In renal cancer cell lines, miR-145 expression was strongly suppressed by methylation. In summary, miR-145 is downregulated in renal cancer patients, which leads to the up-regulation of ADAM17 in renal cancer. Importantly, miR-145 and ADAM17 are regulated in a reciprocal negative feedback loop.

Abbreviations

ADAM
A disintegrin and metalloproteinase
RCC
renal cell carcinoma
TNF
tumor necrosis factor

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1

This article refers to supplementary materials, which are designated by Figures W1 to W3 and are available online at www.neoplasia.com.