Astragalus polysaccharides inhibit ovarian cancer cell growth via microRNA-27a/FBXW7 signaling pathway

Abstract

Astragalus polysaccharide (APS), a natural antioxidant found in Astragalus membranaceus emerging as a novel anticancer agent, exerts antiproliferative and pro-apoptotic activity in various cancer cell types, but its effect on ovarian cancer (OC) remains unknown. In the present study, we tried to elucidate the role and mechanism of APS in OC cells. Our results showed that APS treatment suppressed the proliferation and induced apoptosis in OC cells. Afterward, the microRNA (miRNA) profiles in APS-treated cells were determined by a microarray assay, and whether APS affected OV-90 cells through regulation of miRNA was determined. Among these aberrant miRNAs, miR-27a was selected for further study as its oncogenic roles in various human cancers. Moreover, we found overexpression of miR-27a reversed the antiproliferation and pro-apoptotic effects of APS on OC cells. F-box and WD-40 domain protein 7 (FBXW7), a classical tumor suppressor, was found directly targeted by miR-27a and its translation was suppressed by miR-27a in OC cells. Finally, it was also observed that knockdown of FBXW7 by si-FBXW7 reversed the tumor suppressive activity of APS in OC cells, which is similar to the effects of miR-27a overexpression. Our findings demonstrate that APS can suppress OC cell growth in vitro via miR-27a/FBXW7 axis, and this observation reveals the therapeutic potential of APS for treatment of OC.

FBXW7 inhibits invasion, migration and angiogenesis in ovarian cancer cells by suppressing VEGF expression through inactivation of β‑catenin signaling

“…FBXW7 expression is downregulated in OC tissues, and low FBXW7 expression is negatively associated with the malignant potential of OC (14). Increasing evidence has suggested that FBXW7-knockdown can promote OC cell invasion and migration (36). The results of the present study demonstrated that overexpression of FBXW7 inhibited the invasion, migration, EMT and angiogenesis of OC cells.…”

Mechanisms and Advances in Anti-Ovarian Cancer with Natural Plants Component

“…In both cell lines, miR-27a upregulation obviously reversed the inhibitory effects exhibited by APS, such as antiproliferation and proapoptotic. It produced the same as the effects of knockdown of FBXW7 by si-FBXW7 [ 64 ]. Tanshinone IIA (Tan-IIA) is a natural plant-derived component enriched in Chinese herbal medicine DanShen.…”

Associations of genetic variants of miRNA coding regions with pulmonary tuberculosis risk in China

“…Just as it was reported in the previous study by Mushtaq Ahmad et al, the SNP effects the size of the terminal loop in the precursor miRNA of miR-27a and then modify the common breast cancer risk, which was very common in female population [24]. And in ovarian cancer cell lines, another common female cancer cell line, the F-box and WD-40 domain protein 7 (FBXW7), a classical tumor suppressor, was found directly targeted by miR-27a and its translation was suppressed by miR-27a [25]. Furthermore, Zhang et al found that miR-27a promoted the progression of ovarian cancer cells and induced the process of EMT via the Wnt/β-catenin signalling pathway through inhibition of FOXO1 [26].…”