Department of Pediatric Hematology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
Cell Biol Int. 2018 Jul;42(7):867-876. doi: 10.1002/cbin.10954. Epub 2018 Mar 24.
Neuroblastoma is the most common tumor diagnosed in children and infants, with high recurrence and poor prognosis. Angelica sinensis polysaccharide (AP) whose average molecular weight is 72,900 Da possesses various bioactivities. We aimed to explore the effects of AP on neuroblastoma SH-SY5Y cells as well as the underlying mechanisms. Effects of AP on cell viability, proliferation, apoptosis, migration, invasion, and expressions of long noncoding RNA H19 (lncRNA-H19), microRNA (miR)-675, and CD44 were assessed. Then, effects of miR-675 overexpression on AP-treated cells were analyzed. Next, expression of key kinases in the PI3K/AKT and JAK/ STAT pathways was detected. The possible target gene of miR-675 was finally explored. Cell viability was reduced by 200-500 µg/mL AP. Meanwhile, AP repressed cell proliferation, migration, and invasion, but induced apoptosis. Expressions of lncRNA-H19 and miR-675 were upregulated in neuroblastoma cells, and were downregulated by AP. AP was also identified to upregulate CD44. We next found AP affected SH-SY5Y cells through downregulating miR-675. Key kinases in the PI3K/AKT and JAK/STAT pathways were downregulated by AP stimulation, while these downregulations were abrogated by miR-675 overexpression. KIF1B isoform β (KIF1Bβ) is proved to be a target of miR-675. In conclusion, AP was first identified to inhibit proliferation, migration, and invasion but induce apoptosis. Furthermore, AP might repress tumorigenesis of SH-SY5Y cells through miR-675-mediated inactivation of the PI3K/AKT and JAK/STAT pathways. Besides, KIF1Bβ might be a target of miR-675.
神经母细胞瘤是儿童和婴儿中最常见的肿瘤，具有高复发率和预后不良的特点。当归多糖（AP）的平均分子量为 72900Da，具有多种生物活性。我们旨在探讨 AP 对神经母细胞瘤 SH-SY5Y 细胞的影响及其潜在机制。评估 AP 对细胞活力、增殖、凋亡、迁移、侵袭以及长链非编码 RNA H19（lncRNA-H19）、微小 RNA（miR）-675 和 CD44 的表达的影响。然后，分析过表达 miR-675 对 AP 处理细胞的影响。接着，检测 PI3K/AKT 和 JAK/STAT 通路中关键激酶的表达。最后，探讨了 miR-675 的可能靶基因。浓度为 200-500μg/ml 的 AP 可降低细胞活力。同时，AP 抑制细胞增殖、迁移和侵袭，但诱导凋亡。lncRNA-H19 和 miR-675 的表达在神经母细胞瘤细胞中上调，而 AP 则下调其表达。AP 还上调了 CD44 的表达。我们发现 AP 通过下调 miR-675 影响 SH-SY5Y 细胞。AP 刺激可下调 PI3K/AKT 和 JAK/STAT 通路中的关键激酶，而过表达 miR-675 则可消除这些下调作用。KIF1B 异构体 β（KIF1Bβ）被证明是 miR-675 的靶基因。总之，AP 首次被鉴定为抑制增殖、迁移和侵袭，诱导凋亡。此外，AP 可能通过 miR-675 介导的 PI3K/AKT 和 JAK/STAT 通路失活抑制 SH-SY5Y 细胞的肿瘤发生。此外，KIF1Bβ 可能是 miR-675 的靶基因。
