Cheng Qian, Qu Debao, Lu Zheng, Zhang Longzhen
Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
Department of Radiation Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
Oncol Lett. 2019 Jan;17(1):765-772. doi: 10.3892/ol.2018.9686. Epub 2018 Nov 12.
Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2), a novel cell migration determinant, is able to co-express with other genes of the oxidative phosphorylation pathway by using a computational expression screening technique. However, little is known about the expression and biological function of CHCHD2 in human renal cell carcinoma (RCC). Western blotting was performed to detect CHCHD2 expression levels in normal renal cells and carcinoma cells. Immunohistochemistry was performed to detect an association between CHCHD2 expression and clinicopathological parameters in 75 RCC tissues using a tissue microarray. The function of CHCHD2 in the migration and angiogenesis of RCC cells was investigated using Transwell migration and tube formation assays. CHCHD2 expression was markedly increased in human RCC cells. The results of immunohistochemical analysis revealed that CHCHD2 expression was markedly associated with tumor grade (P<0.001). Notably, CHCHD2 knockdown inhibited RCC migration and tube formation of human umbilical vascular endothelial cells. CHCHD2 knockdown further suppressed matrix metalloproteinase-2 protein levels and enzyme activity. An ELISA identified that CHCHD2 knockdown decreased the secretion of vascular endothelial growth factor. The gathered data disclose information on the association of CHCHD2 with migration and angiogenesis of human RCC, and may strengthen the feasibility of targeting CHCHD2 as a potential therapeutic target.
含卷曲螺旋-螺旋-卷曲螺旋-螺旋结构域蛋白2（CHCHD2）是一种新型的细胞迁移决定因子，通过使用计算表达筛选技术，它能够与氧化磷酸化途径的其他基因共表达。然而，关于CHCHD2在人类肾细胞癌（RCC）中的表达和生物学功能知之甚少。进行蛋白质免疫印迹法检测正常肾细胞和癌细胞中CHCHD2的表达水平。使用组织芯片对75例RCC组织进行免疫组织化学检测，以检测CHCHD2表达与临床病理参数之间的关联。使用Transwell迁移实验和管腔形成实验研究CHCHD2在RCC细胞迁移和血管生成中的功能。CHCHD2在人类RCC细胞中的表达明显增加。免疫组织化学分析结果显示，CHCHD2表达与肿瘤分级显著相关（P<0.001）。值得注意的是，敲低CHCHD2可抑制RCC迁移以及人脐静脉血管内皮细胞的管腔形成。敲低CHCHD2进一步抑制基质金属蛋白酶-2的蛋白水平和酶活性。酶联免疫吸附测定法确定敲低CHCHD2可降低血管内皮生长因子的分泌。收集的数据揭示了CHCHD2与人类RCC迁移和血管生成之间的关联信息，并可能增强将CHCHD2作为潜在治疗靶点的可行性。
