Downregulation of lncRNA ZFAS1 and upregulation of microRNA-129 repress endocrine disturbance, increase proliferation and inhibit apoptosis of ovarian granulosa cells in polycystic ovarian syndrome by downregulating HMGB1.

OBJECTIVE: The objective was to find the role of long-non-coding RNA zinc finger antisense 1 (lncRNA ZFAS1)/microRNA (miR)-129/high-mobility group box protein 1 (HMGB1) axis in polycystic ovary syndrome (PCOS). METHODS: Ovarian granulosa cells from non-PCOS patients and PCOS patients were collected, and HMGB1, miR-129 and lncRNA ZFAS1 expression were detected. Ovarian granulosa cells were transfected with si-ZFAS1 or miR-129 mimics to verify their roles in P4 and E2 secretion, and the biological functions of ovarian granulosa cells. RESULTS: LncRNA ZFAS1 and HMGB1 were elevated, while miR-129 was down-regulated in ovarian granulosa cells of PCOS patients. Down-regulated lncRNA ZFAS1 or overexpressed miR-129 could decrease HMGB1 expression, increase P4 and E2 secretion, promote proliferation activity while inhibit apoptosis of ovarian granulosa cells in PCOS. CONCLUSION: LncRNA ZFAS1 could bind to miR-129 to promote HMGB1 expression, thereby affecting the endocrine disturbance, proliferation and apoptosis of ovarian granulosa cells in PCOS.

Bu Shen Yang Xue Prescription Has Treating Effect on Endometrial Cancer through FSH/PI3K/AKT/Gankyrin/HIF-α/cyclinD 1 Pathway in Ishikawa Cells.

Background. The formulation of Bu Shen Yang Xue (BSYX) has been clinically used in treating gynecologic disease in China, especially for the development of the endometrium. Endometrial carcinoma is the most common malignant tumor of the female genital tract in developed countries. And few studies have been reported on the antitumor activity of BSYX. Therefore, this study aimed to investigate the effect of BSYX on endometrial cancer and make an initial discussion of the underlining mechanisms in Ishikawa cells. Methods and Results. Firstly, 60 SPF female nude mice were randomly divided into control group, model group, BSYX group, and positive group. The models of subcutaneous tumor xenograft of nude mice were established by injection of human endometrial carcinoma cell line Ishikawa tumor cell suspension. Compared with model group, BSYX reduced effectively tumor volume and changed pathological feature in mice tumor issue. Meanwhile, proteins from tumor issues were detected by western blot analysis. The protein levels of follicle-stimulating hormone receptor (FSHR), p-Akt/Akt, Gankyrin, and cyclinD1 in the model group were higher than those in control group but the expression in BSYX group was lower than that in the model group. The hypoxia inducible factor alpha (HIF-α) protein level in the model group was lower than those in control group and upregulated in BSYX group. In addition, Ishikawa cells were cultured and then exposed to follicle-stimulating hormone (FSH), LY294002, a highly selective PI3K inhibitor and serum containing BSYX, respectively. LY294002 and BSYX markedly decreased the cancer cell viability and migration ability and increased the apoptosis rate. FSH promoted the cancer cell ability and migration ability. LY294002 and BSYX evidently downregulated the proteins levels of FSHR, p-Akt/Akt, Gankyrin, and cyclinD1 and upregulated the expression of HIF-α protein, and FSH was on the opposite. Conclusions. Taken together, our results showed that the formulation of BSYX had antitumor effect on endometrial cancer in vivo and in vitro and was related with FSH/PI3K/AKT/Gankyrin/HIF-α/cyclinD1 transduction pathway.