State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
Cancer Res. 2020 May 15;80(10):1957-1969. doi: 10.1158/0008-5472.CAN-19-0334. Epub 2020 Feb 14.
Nasopharyngeal carcinoma is an Epstein-Barr virus (EBV)-related malignancy. Recently, we found that the EBV-encoded miRNA was increased in the serum of patients with preclinical nasopharyngeal carcinoma and that the copy number positively correlated with disease progression. In this study, we established its role in nasopharyngeal carcinoma progression and explored underlying mechanisms and clinical significance. was an independent unfavorable prognostic factor for progression-free survival and its circulating abundance positively associated with distant metastasis. Ectopic expression of promoted migration and invasion of EBV-negative nasopharyngeal carcinoma cells, whereas genetic downregulation of in EBV-positive nasopharyngeal carcinoma cells decreased aggressiveness. Mechanistically, targeted , a negative regulator of Rho signaling. Downregulation of phenocopied the effect of and reconstitution of rescued the phenotype. By suppressing activated Rho signaling to enhance cell motility. These findings suggest a novel role for EBV miRNA in promoting nasopharyngeal carcinoma metastasis and its potential value as a prognostic indicator or therapeutic target. SIGNIFICANCE: This study shows that EBV-encoded BART2-5p miRNA suppresses expression of the RND3 Rho family GTPase, consequently promoting ROCK signaling, cell motility, and metastatic behavior of NPC cells.
鼻咽癌是一种与 EBV（Epstein-Barr 病毒）相关的恶性肿瘤。最近，我们发现 EBV 编码的 microRNA 在临床前鼻咽癌患者的血清中增加，并且其拷贝数与疾病进展呈正相关。在这项研究中，我们确定了其在鼻咽癌进展中的作用，并探讨了其潜在的机制和临床意义。 是无进展生存期的独立不良预后因素，其循环丰度与远处转移呈正相关。 过表达促进 EBV 阴性鼻咽癌细胞的迁移和侵袭，而 EBV 阳性鼻咽癌细胞中 的遗传下调则降低了侵袭性。从机制上讲， 靶向 Rho 信号通路的负调节剂 。下调 模拟了 的作用，而 的重建挽救了表型。通过抑制激活的 Rho 信号来增强细胞迁移。这些发现表明 EBV microRNA 在促进鼻咽癌转移中具有新的作用，并且具有作为预后指标或治疗靶点的潜在价值。意义：本研究表明 EBV 编码的 BART2-5p miRNA 抑制了 RND3 Rho 家族 GTPase 的表达，从而促进了 ROCK 信号、细胞迁移和 NPC 细胞的转移行为。
