RESUMO
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.
Assuntos
MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , RNA Circular/genética , Neoplasias do Colo do Útero/genética , Idoso , Pareamento de Bases , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Biologia Computacional/métodos , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Células HT29 , Humanos , Estimativa de Kaplan-Meier , Luciferases/genética , Luciferases/metabolismo , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , PTEN Fosfo-Hidrolase/metabolismo , RNA Circular/metabolismo , Transdução de Sinais , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologiaRESUMO
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.
Assuntos
Proteínas ADAM/metabolismo , Condrócitos/patologia , Progressão da Doença , Matriz Extracelular/metabolismo , Retroalimentação Fisiológica , Proteínas de Membrana/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Receptor Notch1/metabolismo , Proteínas ADAM/deficiência , Proteínas ADAM/genética , Animais , Linhagem Celular , Receptores ErbB/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Técnicas de Silenciamento de Genes , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , NF-kappa B/metabolismo , Fenótipo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Regulação para CimaRESUMO
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.
Assuntos
Antineoplásicos/uso terapêutico , Tumor Desmoplásico de Pequenas Células Redondas/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Adulto , Antineoplásicos/farmacologia , Biópsia , Tumor Desmoplásico de Pequenas Células Redondas/diagnóstico , Tumor Desmoplásico de Pequenas Células Redondas/metabolismo , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
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.