神经母细胞瘤是起源于原始神经c的恶性肿瘤。环状RNA(circRNA)驱动蛋白超家族蛋白2A(circkif2A,也称为hsa_circ_0129276)已被报道在神经母细胞瘤中上调。然而,circKIF2A参与神经母细胞瘤的分子机制尚不明确。我们分析了circKIF2A的表达水平,microRNA-377-3p(miR-377-3p),和神经母细胞瘤组织和细胞系(SK-N-AS和LAN-6)中的磷酸核糖焦磷酸合成酶1(PRPS1),并探讨了它们的作用。在21例神经母细胞瘤组织和细胞中,CircKIF2A和PRPS1的表达水平升高,miR-377-3p的表达水平降低。功能上,沉默circKIF2A抑制细胞增殖,迁移,入侵,和糖酵解,体外增强神经母细胞瘤细胞凋亡,并阻止裸鼠皮下移植瘤的生长。机械上,circKIF2A可以作为miR-377-3p的海绵来增强PRPS1的表达。CircKIF2A敲低阻碍细胞增殖,转移,和糖酵解部分通过调节miR-377-3p/PRPS1轴,提示靶向circKIF2A可能是神经母细胞瘤的可行治疗策略。
Neuroblastoma is a malignant tumor originating from the primitive neural crest. Circular RNA (circRNA) Kinesin Superfamily Protein 2A (circKIF2A, also known as hsa_circ_0129276) has been reported to be upregulated in neuroblastoma. However, the molecular mechanism of circKIF2A participated in neuroblastoma is poorly defined. We analyzed the expression levels of circKIF2A, microRNA-377-3p (miR-377-3p), and phosphoribosyl pyrophosphate synthetase 1 (
PRPS1) in neuroblastoma tissues and cell lines (SK-N-AS and LAN-6) and explored their roles. The expression levels of CircKIF2A and
PRPS1 were increased and that of miR-377-3p were decreased in 21 neuroblastoma tissues and cells. Functionally, the silencing of circKIF2A inhibited cell proliferation, migration, invasion, and glycolysis, boosted apoptosis in neuroblastoma cells in vitro, and blocked the growth of subcutaneously transplanted tumors in nude mice. Mechanically, circKIF2A could work as a sponge of miR-377-3p to enhance
PRPS1 expression. CircKIF2A knockdown impedes cell proliferation, metastasis, and glycolysis partly by regulating the miR-377-3p/
PRPS1 axis, suggesting that targeting circKIF2A can be a feasible therapeutic strategy for neuroblastoma.