Angelica sinensis polysaccharide inhibits proliferation, migration, and invasion by downregulating microRNA‐675 in human neuroblastoma cell line SH‐SY5Y

Abstract

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.

Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19

“…However, a recent study also showed the inhibitory effects of AP on cell proliferation, migration, and invasion. 41 The results in our study are inconsistent with this study, possibly because of the different cell lines used and the different regulatory mechanisms in the experiments. Further studies are still needed in order to confirm these findings.…”

“…The interesting results revealed that AP increased the expression level of H19 in a dose-dependent manner. However, Yang et al 41 found that expression of H19 was significantly downregulated in AP-treated neuroblastoma cells. Different expression levels of H19 might be due to different cell lines used in the studies.…”

Angelica polysaccharide moderates hypoxia-evoked apoptosis and autophagy in rat neural stem cells by downregulation of BNIP3

“…Coincidentally, Bcl2/adenovirus EIB 19kD-interacting protein 3 (BNIP3) has been reported not only to exert key functions in neural precursor cells (NPCs) but also show potential roles in responding to hypoxiainduced injury [10]. In addition, as the previous literature reported that AP normally achieves its functions through regulating some other factors, such as miR-223 [7], miR-675 [11] and activating transcription factor 6 (ATF6) pathway [12]. Herein, is there possible regulating relationship between AP and BNIP3?…”

A Nano Drug Delivery System Based on Angelica sinensis Polysaccharide for Combination of Chemotherapy and Immunotherapy

“…It has been shown in recent studies that polysaccharides from traditional Chinese medicine (TCM) can improve the immunosuppressive state of tumor microenvironment to play an antitumor effect [1], through regulating T lymphocyte subsets in the tumor microenvironment, promoting the maturation of dendritic cells (DC), activating macrophages, and inhibiting tumor angiogenesis. In our previous researches, it was found that Angelica polysaccharide (AP) could inhibit tumor growth and enhance antitumor immunity [2][3][4][5][6].…”