Jam3 promotes migration and suppresses apoptosis of renal carcinoma cell lines
Jam3 promotes migration and suppresses apoptosis of renal carcinoma cell lines
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DOI：
10.3892/ijmm.2018.3854
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发表时间：
2018-11-01
影响因子：
5.4
通讯作者：
Sun, Jiping
中科院分区：
文献类型：
--
作者：
Li, Xudong;Yin, Aiping;Sun, Jiping
肾细胞癌（RCC）作为肾癌的常见类型，年死亡率很高。在中国和世界范围内，肾细胞癌的发病率一直在增加。大量肾细胞癌病例在晚期才被诊断出来，通常伴有局部和/或系统转移。肾细胞癌的手术切除仅适合少数早期肿瘤患者，因此需要新的治疗方法。连接粘附分子 3 (Jam3) 是连接粘附分子家族的成员，与上皮细胞和癌细胞增殖有关。本研究调查了 Jam3 基因是否通过增殖和凋亡影响肾细胞癌的生长。研究Jam3在肾癌细胞中的表达和生物学功能。通过逆转录聚合酶链反应和蛋白质印迹分析检查 Jam3 的 mRNA 和蛋白质水平。使用小干扰 RNA、伤口愈合测定、流式细胞术和细胞迁移测定确定 Jam3 在肾癌细胞迁移和凋亡中的作用。在细胞迁移测定中，通过蛋白质印迹分析检测了 E-钙粘蛋白、N-钙粘蛋白、整合素 1 和基质金属蛋白酶 (MMP)-2 蛋白。结果显示，与肾小管上皮细胞相比，人肾癌细胞中Jam3的表达显着升高。 Jam3的敲低抑制肾癌细胞迁移并促进肾癌细胞凋亡。它还增加了 E-钙粘蛋白的蛋白质水平，并降低了 N-钙粘蛋白、整合素 1 和 MMP-2 的蛋白质水平。 Jam3 的抑制通过调节 E-cadherin、N-cadherin、integrin 1 和 MMP-2 的表达来促进肾癌细胞的迁移并抑制细胞凋亡。因此，Jam3被建议作为RCC诊断和治疗的新靶基因。
As a common type of renal cancer, renal cell carcinoma (RCC) has a high annual mortality rate. The incidence of RCC has been increasing in China and worldwide. A large number cases of RCC are diagnosed at late stages, often with local and/or systematic metastasis. Surgical resection of RCC is only suitable for a small number of patients with early stage tumors, and thus, novel therapeutic methods are required. Junctional adhesion molecule 3 (Jam3) is a member of the junctional adhesion molecule family, which has been linked to epithelial and cancer cell proliferation. The present study investigated whether the Jam3 gene affected RCC growth via proliferation and apoptosis. The expression and biological function of Jam3 in renal carcinoma cells was investigated. The mRNA and protein levels of Jam3 were examined by reverse transcription-polymerase chain reaction and western blot analyses. The role of Jam3 in the migration and apoptosis of renal carcinoma cells was determined using small interfering RNA, wound-healing assays, flow cytometry, and cell migration assays. In the cell migration assays, E-cadherin, N-cadherin, integrin 1, and matrix metalloproteinase (MMP)-2 proteins were detected by western blot analysis. It was shown that the expression of Jam3 was significantly elevated in human renal carcinoma cells compared with that in renal tubular epithelial cells. The knockdown of Jam3 inhibited renal carcinoma cell migration and promoted renal carcinoma cell apoptosis. It also increased the protein levels of E-cadherin and reduced the protein levels of N-cadherin, integrin 1 and MMP-2. The inhibition of Jam3 promoted migration and suppressed apoptosis of renal carcinoma cells via regulation of the expression of E-cadherin, N-cadherin, integrin 1 and MMP-2. Therefore, Jam3 was suggested as a novel target gene for the diagnosis and treatment of RCC.