Department of Urology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, 110042, China.
Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, China.
Cancer Gene Ther. 2019 Sep;26(9-10):323-333. doi: 10.1038/s41417-018-0064-8. Epub 2018 Nov 21.
Renal cell carcinoma (RCC), which is one of the most diagnosed urological malignancies worldwide, is usually associated with abnormality in both genetic and cellular processes. In the present study, through analyzing The Cancer Genome Atlas (TCGA) dataset, we screened out ERCC6L as a candidate gene that is potentially related to the development of RCC based on its increased expression in ccRCC tissues compared with normal kidney tissues as well as its possible relevance to cancer prognosis. Evidence indicates that ERCC6L is an indispensable component of mammalian cell mitosis, while it fails to disclose the role of ERCC6L in tumorigenesis. By using RT-PCR, it was confirmed that the mRNA expression of ERCC6L was upregulated in RCC tissues as compared to normal controls in 28 pared samples. In addition, the immunohistochemistry study in a tissue microarray (TMA) containing 150 ccRCC samples showed that the staining score of ERCC6L was positively correlated with the Fuhrman grade of cancers. Next, when the expression of ERCC6L was lowered by specific shRNA, the cell viability was significantly inhibited in 786-O and Caki-1 cells, while the apoptosis was induced accordingly. At the same time, RCC cells those were transfected with shRNA targeting to ERCC6L grew significantly slower than parental cells in immunodeficient mice. These results consistently suggest that ERCC6L may play a role in regulating the cell viability of RCC both in vitro and in vivo. Further, gene expression microarray analysis followed by the validating western blot after knocking down ERCC6L expression in 786-O cells highlighted the involvement of MAPK signaling pathway in regulation of ERCC6L on cellular process of RCC. In conclusion, the present study suggests a likely promoting role of ERCC6L on the development of RCC. Thus, further study to explore the potential utility of ERCC6L as a novel therapeutic target of RCC is clearly needed.
肾细胞癌（RCC）是全球最常见的泌尿系统恶性肿瘤之一，通常与遗传和细胞过程的异常有关。在本研究中，通过分析癌症基因组图谱（TCGA）数据集，我们筛选出 ERCC6L 作为候选基因，其在 ccRCC 组织中的表达高于正常肾脏组织，并且可能与癌症预后相关。有证据表明，ERCC6L 是哺乳动物细胞有丝分裂不可或缺的组成部分，但其在肿瘤发生中的作用尚不清楚。通过 RT-PCR，在 28 对配对样本中证实，RCC 组织中 ERCC6L 的 mRNA 表达水平高于正常对照。此外，在包含 150 例 ccRCC 样本的组织微阵列（TMA）的免疫组织化学研究表明，ERCC6L 的染色评分与癌症的 Fuhrman 分级呈正相关。接下来，当特异性 shRNA 降低 ERCC6L 的表达时，786-O 和 Caki-1 细胞的细胞活力显著受到抑制，同时诱导细胞凋亡。同时，转染靶向 ERCC6L 的 shRNA 的 RCC 细胞在免疫缺陷小鼠中生长速度明显慢于亲本细胞。这些结果一致表明，ERCC6L 可能在体外和体内调节 RCC 细胞活力中发挥作用。进一步的基因表达微阵列分析后，在 786-O 细胞中敲低 ERCC6L 表达后的验证性 Western blot 强调了 MAPK 信号通路在调节 ERCC6L 对 RCC 细胞过程中的作用。总之，本研究表明 ERCC6L 可能在 RCC 的发生发展中起促进作用。因此，需要进一步研究探索 ERCC6L 作为 RCC 新型治疗靶点的潜在应用价值。
