Glioma is highly lethal because of its high malignancy. Ubiquitination, a type of ubiquitin-dependent protein modification, has been reported to play an oncogenic or tumor-suppressive role in glioma development, depending on the targets. Ring finger protein 139 (RNF139) is a membrane-bound E3 ubiquitin ligase serving as a tumor suppressor by ubiquitylation-dependently suppressing cell growth. Herein, we firstly confirmed the abnormal downregulation of RNF139 in glioma tissues and cell lines. In glioma cells, ectopic RNF139 overexpression could inhibit, whereas RNF139 knockdown could aggravate the aggressive behaviors of glioma cells, including hyperproliferation, migration, and invasion. Moreover, in two glioma cell lines, RNF139 overexpression inhibited, whereas RNF139 knockdown enhanced the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and AKT serine/threonine kinase 1 (AKT). In a word, we demonstrate the aberration in RNF139 expression in glioma tissue samples and cell lines. RNF139 serves as a tumor-suppressor in glioma by inhibiting glioma cell proliferation, migration, and invasion and promoting glioma cell apoptosis through regulating PI3K/AKT signaling.

神经胶质瘤由于其恶性程度高而具有高度致命性。据报道，泛素化是一种泛素依赖性蛋白质修饰，根据靶标的不同，它在胶质瘤的发展中发挥致癌或抑制肿瘤的作用。环指蛋白 139 (RNF139) 是一种膜结合的 E3 泛素连接酶，通过泛素化依赖性抑制细胞生长作为肿瘤抑制因子。在此，我们首先证实了神经胶质瘤组织和细胞系中 RNF139 的异常下调。在胶质瘤细胞中，异位 RNF139 过表达可以抑制，而 RNF139 敲低可以加剧胶质瘤细胞的侵袭行为，包括过度增殖、迁移和侵袭。此外，在两种神经胶质瘤细胞系中，RNF139 过表达受到抑制，而 RNF139 敲低增强了磷脂酰肌醇 3-激酶 (PI3K) 和 AKT 丝氨酸/苏氨酸激酶 1 (AKT) 的磷酸化。总之，我们证明了神经胶质瘤组织样本和细胞系中 RNF139 表达的异常。RNF139通过抑制胶质瘤细胞增殖、迁移和侵袭，通过调节PI3K/AKT信号促进胶质瘤细胞凋亡，在胶质瘤中起到抑癌作用。