Phosphatase and Tensin Homology Deletion Gene (PTEN) Regulates Fibroblast Precursor Cells Autophagy and Vascular Endothelial Growth Factor Signaling in Preeclampsia

Preeclampsia (PE) causes serious harm to the health of mothers and infants. PTEN regulates cell biological behaviors, but its role in preeclampsia have not been reported. Real time PCR and Western blot detected PTEN level in the placenta of PE patients and controls. Placental trophoblastderived cell line HTR8 was assigned into NC group, PTEN group and si-PTEN inhibitor group followed by measuring PTEN level, cell proliferation by MTT assay, cell invasion by Transwell, Caspase 3 activity, Beclin-1 and Atg-5 expression as well as PI3K/Akt/HIF-1α/VEGF signaling protein by Western blot. PTEN in PE patients was significantly downregulated (P < 0.05). Transfection of PTEN siRNA significantly down-regulated PTEN, promoted cell proliferation and invasion, reduced Caspase 3 activity, increased Beclin-1 and Atg-5, and PI3K/Akt/HIF-1α/VEGF protein expression (P < 0.05). Transfection of pcDNA 3.0-PTEN up-regulated PTEN and significantly reversed the above changes (P < 0.05). In conclusion, PTEN is reduced in PE and it can regulate pre-eclampsia trophoblast autophagy possibly through PI3K/Akt/HIF-1α/VEGF signaling, suggesting that PTEN can be a potential target for PE therapy.

Clues for Improving the Pathophysiology Knowledge for Endometriosis Using Serum Micro-RNA Expression

The pathophysiology of endometriosis remains poorly understood. The aim of the present study was to investigate functions and pathways associated with the various miRNAs differentially expressed in patients with endometriosis. Plasma samples of the 200 patients from the prospective “ENDO-miRNA” study were analyzed and all known human miRNAs were sequenced. For each miRNA, sensitivity, specificity, and ROC AUC values were calculated for the diagnosis of endometriosis. miRNAs with an AUC ≥ 0.6 were selected for further analysis. A comprehensive review of recent articles from the PubMed, Clinical Trials.gov, Cochrane Library, and Web of Science databases was performed to identify functions and pathways associated with the selected miRNAs. In total, 2633 miRNAs were found in the patients with endometriosis. Among the 57 miRNAs with an AUC ≥ 0.6: 20 had never been reported before; one (miR-124-3p) had previously been observed in endometriosis; and the remaining 36 had been reported in benign and malignant disorders. miR-124-3p is involved in ectopic endometrial cell proliferation and invasion and plays a role in the following pathways: mTOR, STAT3, PI3K/Akt, NF-κB, ERK, PLGF-ROS, FGF2-FGFR, MAPK, GSK3B/β–catenin. Most of the remaining 36 miRNAs are involved in carcinogenesis through cell proliferation, apoptosis, and invasion. The three main pathways involved are Wnt/β–catenin, PI3K/Akt, and NF–KB. Our results provide evidence of the relation between the miRNA profiles of patients with endometriosis and various signaling pathways implicated in its pathophysiology.

Astragalus Polysaccharides Alleviate Lung Adenocarcinoma Bone Metastases by Inhibiting the CaSR/PTHrP Signaling Pathway

Background: To expore the possible effect and mechanism of Astragalus Polysaccharide (APS) on bone metastasis of lung adenocarcinoma.Methods: The culture media of osteoclast (OC) precursor cells, osteoblasts (OBs) and A549 cells were constructed respectively. TRAP staining was used to detect the effect of APS on OC differentiation. Alizarin red staining was used to detect the effect of APS on OB differentiation. The expressions of OC differentiation related proteins and OB specific proteins were detected by Western blotting. The effects of APS on the proliferation and migration of A549 cells were detected by CCK-8 and Transwell assay, respectively. The effect of APS on A549 induced apoptosis was analyzed by flow cytometry. The expression of calcium sensing receptor (CaSR) / parathyroid hormone-related protein (PTHrP) signal pathway related proteins was detected by Western blotting. The mouse model of bone metastasis of lung adenocarcinoma was established. The occurrence of bone metastasis of lung adenocarcinoma in mice was verified by micro CT. The inhibition of APS on bone metastasis and the promotion of tumor cell apoptosis were detected by HE staining and TUNEL assay.Results: APS inhibited the formation of receptor activator of nuclear factor-κB ligand (RANKL) induced OCs and promoted the differentiation of OBs in a concentration dependent manner. APS inhibited RANKL induced OC differentiation and the expression of related proteins, and promoted OB differentiation and the expression of related proteins. APS inhibited the proliferation and migration of A549 cells and promoted apoptosis in a concentration dependent manner. APS may inhibit the proliferation and invasion of A549 cells by inhibiting CaSR / PTHrP signaling pathway, and inhibit the expression of CaSR / PTHrP signaling pathway related proteins. In vivo experiments confirmed that APS inhibited bone metastasis of lung adenocarcinoma.Conclusions: APS can inhibit the proliferation and invasion of lung adenocarcinoma cells by inhibiting the CaSR / PTHrP pathway, and then affect the balance of OCs and OBs in the bone microenvironment, so as to protect the bone metastasis of lung adenocarcinoma.

CircPIK3C2A Facilitates the Progression of Glioblastoma via Targeting miR-877-5p/FOXM1 Axis

Glioblastoma is a rare yet lethal type of tumor that poses a crucible for the medical profession, owing to its rapid proliferation and invasion resulting in poor prognosis. Circular RNAs (circRNAs), a subclass of regulatory RNAs, are implicated in the regulation of cancerous progression. This study aims to investigate the roles and underlying mechanism of circPIK3C2A in regulating proliferation and invasion of glioblastoma. qRT-PCR assays showed that the expression level of circPIK3C2A was aberrantly higher in glioblastoma cell lines, in comparison with that in normal glia cells. The ectopic expression of circPIK3C2A promoted the proliferation, invasion and clonal formation of glioblastoma cells, while circPIK3C2A loss-of-function exerted exactly the opposite biological effects on the cells. The construction of subcutaneous xenograft tumor model in nude mice indicated that circPIK3C2A loss-of-function effectively diminished tumor load in vivo and prolonged the survival time of tumor-bearing animals. Luciferase reporter assay confirmed the interaction among circPIK3C2A/miR-877-5p and FOXM1. CircPIK3C2A function as competitive endogenous RNA via sponging miR-877-5p through certain binding sites, thereby modulating the expression of FOXM1. Our results collectively indicate that circPIK3C2A functions as ceRNA by mediating miR-877-5p/FOXM1 axis, providing a novel perspective of applying CircPIK3C2A in the clinical intervention of glioblastoma in the future.