Department of Urology, Guangdong Second Provincial General Hospital, The Third Clinical Medical College of Southern Medical University, Guangzhou, Guangdong, China.
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Dis Markers. 2017;2017:8276939. doi: 10.1155/2017/8276939. Epub 2017 Sep 30.
FBXW7, known as a general tumor suppressor, is commonly lowly expressed in metastatic malignancies. We aim to investigate the potential influence of FBXW7 overexpression on renal cell carcinoma (RCC) metastasis.
We employed quantitative real-time PCR (qRT-PCR) and Western blotting (WB) to quantify the FBXW7 expression in RCC cell lines. Upregulation of FBXW7 was performed on RCC cells using the lentivirus covering coding region FBXW7 cDNA sequence, and functional tests were performed to verify FBXW7 overexpression on migration and invasion of RCC cells. Moreover, WB was employed to determine the expressions of MMP-2, MMP-9, and MMP-13, as well as EMT markers in the transfected RCC cells.
FBXW7 was significantly downregulated in RCC cell lines, dominated by 786-O and ACHN, when compared to normal renal cell line HK-2. Moreover, upregulation of FBXW7 in 786-O and ACHN cell lines significantly inhibited cell migration and invasion, as well as EMT. Present study also showed that FBXW7 was involved in the migration and invasion of RCC cells via regulating the expressions of MMP-2, MMP-9, and MMP-13.
Our findings demonstrate that upregulation of FBXW7 inhibits RCC metastasis and EMT. FBXW7 is a potential therapeutic target for RCC patients.
FBXW7 作为一种普遍的抑癌基因，在转移性恶性肿瘤中常低表达。我们旨在研究 FBXW7 过表达对肾细胞癌（RCC）转移的潜在影响。
我们采用实时定量 PCR（qRT-PCR）和 Western blot（WB）来量化 RCC 细胞系中 FBXW7 的表达。使用覆盖 FBXW7 cDNA 序列编码区的慢病毒上调 RCC 细胞中的 FBXW7，并进行功能测试以验证 FBXW7 过表达对 RCC 细胞迁移和侵袭的影响。此外，WB 用于确定转染的 RCC 细胞中 MMP-2、MMP-9 和 MMP-13 以及 EMT 标志物的表达。
与正常肾细胞系 HK-2 相比，RCC 细胞系（以 786-O 和 ACHN 为主）中 FBXW7 的表达显著下调。此外，在 786-O 和 ACHN 细胞系中上调 FBXW7 显著抑制了细胞迁移和侵袭以及 EMT。本研究还表明，FBXW7 通过调节 MMP-2、MMP-9 和 MMP-13 的表达参与 RCC 细胞的迁移和侵袭。
我们的研究结果表明，上调 FBXW7 抑制了 RCC 的转移和 EMT。FBXW7 可能是 RCC 患者的一个潜在治疗靶点。
