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去整合素和金属蛋白酶结构域蛋白 9（ADAM9）表达与膀胱癌恶性程度的相关性。

Relevance of A Disintegrin and Metalloproteinase Domain-Containing (ADAM)9 Protein Expression to Bladder Cancer Malignancy.

机构信息

Department of International Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142, Japan.

International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.

出版信息

Biomolecules. 2022 Jun 6;12(6):791. doi: 10.3390/biom12060791.

DOI:10.3390/biom12060791
PMID:35740916
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9221013/
Abstract

We evaluated the effect of A Disintegrin and Metalloproteinase Domain-Containing (ADAM)9 protein on exacerbation in bladder cancer KK47 and T24. First, we knocked down ADAM9 and investigated cell proliferation, migration, cell cycle, and the epithelial-mesenchymal transition (EMT)-related proteins expression in vitro. We then investigated the expression level of ADAM9 in clinical urine cytology samples and the Cancer Genome Atlas (TCGA) data. Cell proliferation was significantly reduced in both cell lines after ADAM9 knockdown. In the cell-cycle assay, the percentage of G0/G1 cells was significantly increased in ADAM9 knockdown T24. Migration of T24 was more strongly suppressed than KK47. The expression level of EMT-related proteins suggested that EMT was suppressed in ADAM9 knockdown T24. TCGA analysis revealed that ADAM9 mRNA expression was significantly higher in stage IV and high-grade cancer than in other stages and low-grade cancer. Moreover, in the gene expression omnibus (GEO) study, bladder cancer with surrounding carcinoma and invasive carcinoma showed significantly high ADAM9 mRNA expression. We found that ADAM9 knockdown suppressed cell proliferation and migration in bladder cancer and that high-grade bladder cancer is correlated with higher expression of ADAM9.

摘要

我们评估了去整合素和金属蛋白酶结构域蛋白 9（ADAM9）蛋白对膀胱癌 KK47 和 T24 恶化的影响。首先，我们敲低了 ADAM9，并在体外研究了细胞增殖、迁移、细胞周期和上皮-间充质转化（EMT）相关蛋白的表达。然后，我们研究了临床尿液细胞学样本和癌症基因组图谱（TCGA）数据中 ADAM9 的表达水平。ADAM9 敲低后，两种细胞系的细胞增殖均显著减少。在细胞周期分析中，ADAM9 敲低的 T24 中 G0/G1 期细胞的比例显著增加。T24 的迁移比 KK47 更受抑制。EMT 相关蛋白的表达水平表明，ADAM9 敲低抑制了 T24 的 EMT。TCGA 分析显示，IV 期和高级别癌症的 ADAM9 mRNA 表达明显高于其他分期和低级别癌症。此外，在基因表达综合数据库（GEO）研究中，伴有周围癌和浸润性癌的膀胱癌显示出明显高的 ADAM9 mRNA 表达。我们发现 ADAM9 敲低抑制了膀胱癌的细胞增殖和迁移，高级别膀胱癌与 ADAM9 表达升高相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/3ffcc8ab1e4f/biomolecules-12-00791-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/5cc7054b02b8/biomolecules-12-00791-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/ecbab0eeb6f9/biomolecules-12-00791-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/497fb63bb377/biomolecules-12-00791-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/c0848c93f4e3/biomolecules-12-00791-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/5e0249beaed8/biomolecules-12-00791-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/6ea7e0c8e58b/biomolecules-12-00791-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/3ffcc8ab1e4f/biomolecules-12-00791-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/5cc7054b02b8/biomolecules-12-00791-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/ecbab0eeb6f9/biomolecules-12-00791-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/497fb63bb377/biomolecules-12-00791-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/c0848c93f4e3/biomolecules-12-00791-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/5e0249beaed8/biomolecules-12-00791-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/6ea7e0c8e58b/biomolecules-12-00791-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fa/9221013/3ffcc8ab1e4f/biomolecules-12-00791-g007.jpg

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