ABSTRACT
BACKGROUND: MicroRNAs are endogenous small noncoding RNAs, which play a critical role in regulating various biological and pathologic processes. Furthermore, miR-301a has been detected to be overly expressed in tumorigenic progression of ovarian cancer. However, the effects of miR-301a on ovarian cancer are still unclear. OBJECTIVE: The objective of this study is to investigate the molecular mechanisms of miR-301a in epithelial ovarian cancer cells. METHODS: The miR-301a expression in ovarian cancer cells was detected. Then, cell proliferation, cell cycle, and apoptosis of the miR-301a-mimic-transfected ovarian cancer cells were determined, as well as the effects of the miR-301a mimic on the PTEN/phosphoinositide 3-kinase (PI3K) signaling pathway were explored. RESULTS: We found that the miR-301a expression levels were markedly upregulated in ovarian cancer tissues and cells, and upregulation of miR-301a-promoted cell viability and proliferation. Our results also showed that the miR-301a-mimic accelerated cell cycle progression of ovarian cancer cells by targeting the CDK4/Cyclin-D1 pathway but not the CDK2/Cyclin-E pathway. Moreover, transfection of the miR-301a mimic into ovarian cancer cells could decrease the PTEN expression while increasing the PI3K and Akt phosphorylation, as compared with the miR-301a inhibitor group and the negative control group. CONCLUSION: Therefore, miR-301a should be an oncogene in ovarian cancer, and overexpression of miR-301a promoted proliferation of ovarian cancer cells by modulating the PTEN/PI3K/Akt signaling pathway.
Subject(s)
Apoptosis/physiology , Cell Proliferation/physiology , MicroRNAs/physiology , Ovarian Neoplasms/pathology , Signal Transduction/physiology , Carcinoma, Ovarian Epithelial , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Ovarian Neoplasms/genetics , PTEN Phosphohydrolase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , TransfectionABSTRACT
BACKGROUND: Women transitioned to postmenopausal status experience a corresponding gain in iron stores. Recently clinical researches have observed increased serum ferritin level in postmenopausal women, and ferritin level was negatively correlated with bone mineral density. PURPOSE: To explore the mechanism of iron-induced osteopenia in mouse model. METHODS: Briefly, in this study, we established an iron accumulation mouse model with ovariectomy. Primary osteoclasts and osteoblasts were extracted for this research. Biomarkers of bone metabolism and cell signaling pathways were measured. RESULTS: We found that bone mass changed later than ferritin and decreased gradually following overiectomy. We also observed higher levels of bone resorption and oxidative stress when iron was administered. When stimulated with iron, primary osteoclasts derived from bone marrow-derived macrophages (BMMs) underwent differentiation and numerous reactive oxygen species (ROS) were generated. Further, we found that iron activated the JNK, ERK and NF-κB signaling pathways in vivo. In vitro, we found that only NF-κB signaling was stimulated by iron and that suppression of this pathway blocked osteoclast differentiation. To determine whether these effects were related to ROS, osteoclasts were treated with H2O2. We found that ROS stimulated osteoclast activity, and that this effect was reversed upon NF-κB suppression. CONCLUSIONS: These data suggest that ROS might be a downstream factor of iron and regulated NF-κB signaling in osteoclasts in mouse model.
Subject(s)
Cell Differentiation/drug effects , Iron/pharmacology , NF-kappa B/metabolism , Osteoclasts/drug effects , Oxidative Stress/drug effects , Animals , Bone Resorption/etiology , Bone Resorption/metabolism , Cells, Cultured , Female , Mice , Mice, Inbred ICR , Models, Animal , Osteoclasts/physiology , Ovariectomy , Reactive Oxygen Species/metabolism , Signal Transduction/drug effectsABSTRACT
The effects of soybean oligosaccharides (SBOS) on antioxidant enzyme activities and insulin resistance in pregnant women with gestational diabetes mellitus (GDM) were investigated. Ninety-seven pregnant women with GDM were randomly divided into two groups, the control group (51 cases) and the SBOS group (46 cases). Before the group separation, the blood sugar level in patients was maintained stable by regular diet and insulin treatment. The control group was continued with the insulin treatment, while the SBOS group was treated with the combination of insulin and SBOS. Results showed that SBOS were able to reduce oxidative stress and alleviate insulin resistance in pregnant women with GDM, which indicates that SBOS may play an important role in the control of GDM complications.
