Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China.
Department of Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Cancer Med. 2018 Aug;7(8):3862-3874. doi: 10.1002/cam4.1552. Epub 2018 Jun 24.
Rho GTPase-activating protein 42 was identified as an inhibitor of RhoA to maintain normal blood pressure homeostasis. However, the effect of ARHGAP42 in promoting cell malignancy in nasopharyngeal carcinoma is demonstrated in this study. Microarray and real-time quantitative PCR were used for a mRNA profiling of ARHGAP42 in nasopharyngeal primary and metastatic carcinoma tissues. Western blot and immunohistochemical staining were used for detecting the expression of ARHGAP42 protein in nasopharyngeal carcinoma tissues and cell lines. The overexpression and silence experiments of ARHGAP42 were performed in NPC cell lines using siRNA and expressive plasmid for evaluating cancer cell migration and invasion in vitro. Real-time quantitative PCR, western blot, and transwell test were employed for with the function of ARHGAP42 and its antisense lncRNA uc010rul. We confirmed the elevated expression of ARHGAP42 in metastatic NPC tissues of mRNA and protein for the first time. Immunohistochemical analysis indicated that NPC patients with highly ARHGAP42 expression were significantly associated with shorter metastasis-free survival. Knockdown of ARHGAP42 resulted in significant inhibition of nasopharyngeal cancer cell migration and invasion in vitro, and the overexpression of ARHGAP42 showed the opposite effects. In addition, the silence of uc010rul resulted in ARHGAP42 expression decrease and significant inhibition of nasopharyngeal cancer cell migration and invasion. High expression of ARHGAP42 is associated with poor metastasis-free survival of nasopharyngeal carcinoma patients. ARHGAP42 promotes migration and invasion of nasopharyngeal carcinoma cells in vitro; the antisense lncRNA may be involved in this effect.
Rho GTPase 激活蛋白 42 被鉴定为 RhoA 的抑制剂，以维持正常的血压稳态。然而，本研究表明 ARHGAP42 在促进鼻咽癌细胞恶性转化方面具有重要作用。通过微阵列和实时定量 PCR 对鼻咽癌原发和转移癌组织中的 ARHGAP42 mRNA 进行了谱分析。Western blot 和免疫组织化学染色用于检测鼻咽癌组织和细胞系中 ARHGAP42 蛋白的表达。使用 siRNA 和表达质粒在 NPC 细胞系中进行 ARHGAP42 的过表达和沉默实验，以评估体外癌细胞迁移和侵袭。实时定量 PCR、Western blot 和 Transwell 试验用于研究 ARHGAP42 及其反义 lncRNA uc010rul 的功能。我们首次证实 ARHGAP42 在转移性 NPC 组织中的 mRNA 和蛋白表达水平升高。免疫组织化学分析表明，ARHGAP42 高表达的 NPC 患者与无转移生存时间明显缩短相关。ARHGAP42 的敲低导致体外鼻咽癌细胞迁移和侵袭的显著抑制，而过表达 ARHGAP42 则表现出相反的效果。此外，uc010rul 的沉默导致 ARHGAP42 表达降低，并显著抑制鼻咽癌细胞的迁移和侵袭。ARHGAP42 高表达与鼻咽癌患者无转移生存时间较差相关。ARHGAP42 促进体外鼻咽癌细胞的迁移和侵袭；反义 lncRNA 可能参与了这一效应。
