Department of Orthopedics, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road, NO.22, Nanning, Guangxi 530021, China.
Department of Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, University East Road, NO.166, Nanning, Guangxi 530007, China.
Biosci Rep. 2020 Apr 30;40(4). doi: 10.1042/BSR20200282.
Osteosarcoma (OS) is a malignant tumor commonly observed in children and adolescents. Developmentally regulated GTP-binding protein (DRG) 1 plays an important role in embryonic development; aberrantly expressed DRG1 has been associated with pathological processes in cancer. The present study aimed to explore the role of DRG1 in OS and the mechanisms underlying DRG1 overexpression in OS. Clinical studies were performed to evaluate Drg1 expression in OS tissues and to identify a correlation between Drg1 expression and the clinicopathological features in patients with OS. Drg1 was knocked down in OS cells to determine its effects on cell viability, cell cycle distribution, apoptosis, migration, invasion, and colony formation rate. METTL3 and ELAVL1 were also silenced to determine their effects on the levels of N6-methyladenosine (m6A), RNA stability, and Drg1 expression. Higher levels of Drg1 mRNA and protein were observed in OS tissues than those in paracancerous tissues. High expression of DRG1 was associated with large tumor size and advanced clinical stages in OS. Silencing of Drg1 resulted in decreased viability and inhibition of the migration and colony formation abilities of OS cells; it also resulted in cell cycle arrest in the G2/M stage and induced apoptosis. Knockdown of METTL3 led to decreased m6A and Drg1 mRNA levels. ELAVL1 knockdown impaired the stability of DRG1 mRNA, thereby reducing both the mRNA and protein levels of DRG1. In all, DRG1 exerted tumorigenic effects in OS, and the up-regulation of DRG1 in OS was induced by METTL3 and ELAVL1 in an m6A-dependent manner.
骨肉瘤（OS）是一种常见于儿童和青少年的恶性肿瘤。发育调节 GTP 结合蛋白（DRG）1 在胚胎发育中起着重要作用；异常表达的 DRG1 与癌症的病理过程有关。本研究旨在探讨 DRG1 在 OS 中的作用及其在 OS 中过表达的机制。进行了临床研究以评估 OS 组织中的 Drg1 表达，并确定 Drg1 表达与 OS 患者的临床病理特征之间的相关性。敲低 OS 细胞中的 Drg1 以确定其对细胞活力、细胞周期分布、细胞凋亡、迁移、侵袭和集落形成率的影响。还沉默了 METTL3 和 ELAVL1 以确定它们对 N6-甲基腺苷（m6A）水平、RNA 稳定性和 Drg1 表达的影响。与癌旁组织相比，OS 组织中观察到更高水平的 Drg1 mRNA 和蛋白。DRG1 的高表达与 OS 中的大肿瘤大小和晚期临床分期相关。沉默 Drg1 导致 OS 细胞活力降低，迁移和集落形成能力受到抑制；它还导致细胞周期停滞在 G2/M 期并诱导细胞凋亡。沉默 METTL3 导致 m6A 和 Drg1 mRNA 水平降低。ELAVL1 沉默损害了 DRG1 mRNA 的稳定性，从而降低了 DRG1 的 mRNA 和蛋白水平。总之，DRG1 在 OS 中发挥致瘤作用，并且 OS 中 DRG1 的上调是由 METTL3 和 ELAVL1 以 m6A 依赖性方式诱导的。
