Circular RNA hsa_circ_0000730 restrains cell proliferation, migration, and invasion in cervical cancer through miR-942-5p/PTEN axis.

Circular RNAs (circRNAs) play prominent roles in regulating the progression of cancers. This study is aimed to decipher the role of hsa_circ_0000730 in cervical cancer (CC).The differentially expressed circRNAs of CC were screened out from the Gene Expression Omnibus database. qRT-PCR was used to detect circ_0000730 expression in CC tissues and cell lines, and the Kaplan-Meier curve was adopted to figure out the relationship between circ_000730 expression and the overall survival time of CC patients. BrdU assay and Tanswell assay were utilized to examine the proliferation, migration, and invasion of CC cells. Western blot was adopted to detect PTEN protein expression. Bioinformatics analysis and dual-luciferase reporter assay were used to examine the target relationship between miR-942-5p and circ_0000730 or PTEN, respectively.Circ_0000730 was among the differentially expressed circRNAs in CC. Circ_0000730 was significantly down-regulated in the cancer tissues of 50 CC patients and CC cell lines. Additionally, underexpression of circ_0000730 was associated with the shorter survival time of CC patients. Gain- and loss-of-function assays highlighted that circ_0000730 significantly inhibited the proliferation, migration, and invasion of CC cells. Mechanistically, miR-942-5p was identified as a downstream target of circ_0000730, and circ_0000730 could positively regulate PTEN expression via repressing miR-942-5p in CC cells.Circ_0000730 inhibits the proliferation, migration, and invasion of CC cells via regulating miR-942-5p/PTEN axis. Circ_0000730 probably acts as a tumor suppressor in CC, and it may be a candidate target for the treatment of CC.

Notch1-ADAM8 positive feed-back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progression.

BACKGROUND: Osteoarthritis (OA) is one of the most prevalent joint disease, and there are still no effective therapeutic agents or clinical methods for the cure of this disease to date. The degradation of cartilage extracellular matrix (ECM) is a major cause of OA. METHOD: IL-1ß was used to induce chondrogenic degradation. Q-PCR and Western blotting were used to detect mRNA and protein level, respectively. ELISA was used to detect the secreted TNF-α and IL-6 level. Immunofluorescence was used to detect the protein level of Aggrecan, Collagen II and ki67. TUNEL and flow cytometry were used to examine cell apoptosis of chondrocytes. ChIP and luciferase assay were used to study molecular gene regulation. Osteoarthritic animal model and Safranin-O staining were used to determine the in vivo OA phenotype. RESULTS: The expression of ADAM8 was up-regulated in osteoarthritic chondrocytes. Knockdown of ADAM8 suppressed the OA phenotype in the in vitro OA cell model. ADAM8 regulated OA progression through the activation of EGFR/ERK/NF-κB signaling pathway. Inhibition of Notch signaling suppressed OA phenotype in the in vitro OA cell model. Notch signaling regulated the gene expression of ADAM8 directly via Hes1. Notch1-ADAM8 positive feedback loop promoted the progression of OA in vivo. CONCLUSION: Notch1-ADAM8 feed-back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progression.

Effective treatment of apatinib in desmoplastic small round cell tumor: a case report and literature review.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare malignant sarcoma with poor prognosis due to lack of effective treatments. Apatinib is a new potent oral small-molecule tyrosine kinase inhibitor, and targets the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2). In this study, we presented a case of intra-abdominal DSRCT which was effectively treated by apatinib. CASE PRESENTATION: A 32-year-old man was admitted due to increasing urination frequency and palpable mass in right lower abdomen for 2 months. The mass was resected and diagnosed DSRCT. The patient refused chemotherapy and radiotherapy,and used Chinese medicine only. Six months after the surgery, the patient re-hospitalized due to growing abdominal mass and ascites. Intraperitoneal cisplatin treatment showed little effect. Apatinib was then recommended. Apatinib revealed outstanding effect on reducing mass size and ascites during 2-month treatment. Apatinib therapy continued for additional 2 months, and the patient was in good condition. The only toxicity was hand-food syndrome, which was controllable and well tolerated. CONCLUSION: It is the first report that apatinib is effective on DSRCT. This report may provide an additional option for the treatment of metastatic DSRCT.

Overexpression of GLP-1 receptors suppresses proliferation and cytokine release by airway smooth muscle cells of patients with chronic obstructive pulmonary disease via activation of ABCA1.

Glucagon-like peptide-1 (GLP­1) is an important insulin secretagogue that possesses anti­inflammatory effects. GLP­1 receptor (GLP­1R) agonists have been demonstrated to serve a pivotal role in the treatment of obstructive lung diseases, including chronic obstructive pulmonary disease (COPD). However, the specific function and underlying mechanisms of GLP­1R in COPD remain uncertain. The aim of the present study was to investigate the action and underlying mechanisms of GLP­1R in airway smooth muscle (ASM) cells from COPD patients. GLP­1R expression levels were markedly decreased in ASM cells from COPD patients compared with those from healthy controls. ASM cell proliferation and migration, and the levels of the inflammatory cytokines interleukin (IL)­1ß, IL­4, tumor necrosis factor (TNF)­α, and granulocyte­macrophage colony­stimulating factor (GM­CSF) were measured. Transfection of pcDNA3.1­GLP­1R had inhibitory effects on ASM cell proliferation and migration, whereas GLP­1R small interfering (si)RNA reversed these effects. Furthermore, the present study demonstrated that GLP­1R overexpression markedly suppressed IL­1ß, IL­4, TNF­α and GM­CSF levels. GLP­1R overexpression upregulated the expression levels of adenosine triphosphate­binding cassette, subfamily A, member 1 (ABCA1) in ASM cells, and the effects of GLP­1R on cell proliferation and migration, and inflammatory cytokine expression in ASM cells was abolished by siRNA­mediated silencing of ABCA1. The results of the present study suggested that GLP­1R contributes to COPD pathology, potentially via an ABCA1­mediated pathway.