RESUMO
Long noncoding RNA (lncRNA) colon cancer-associated transcript 2 (CCAT2) has been demonstrated to play an important role in diverse tumorigenesis. However, the biological function of lncRNAs in glioma is still unknown. In this study, we found that lncRNA CCAT2 was overexpressed in glioma tissues and cell lines and associated with tumor grade and size. Furthermore, patients with high levels of lncRNA CCAT2 had poorer survival than those with lower levels of lncRNA CCAT2. Knocking down lncRNA CCAT2 expression significantly suppressed the glioma cell growth, migration, and invasion, as well as induced early apoptosis of glioma cells in vitro. Moreover, lncRNA CCAT2 regulated epithelialmesenchymal transition (EMT)-associated gene expression. In conclusion, lncRNA CCAT2 plays an important role in glioma tumorigenesis and progression and may act as a potential biomarker for therapeutic strategy and prognostic prediction.
RESUMO
Contact urticaria is recognized as the wheal and flare reaction at a site from direct contact with a chemical or protein agent. Ongoing studies have proposed that gene silencing may have a promising future in finding optimal treatment of a variety of disease; hence, the aim of the study was to investigate the effect of RNA interference-mediated E-selectin ( SELE) gene silencing on cell adhesion molecule expression and on cell-cell adhesion in vascular endothelial cells (VECs) in a mouse model of immunologic contact urticaria (ICU). Following the successful establishment of mouse models of ICU induced by antidinitrophenol immunoglobulin E (IgE) combining 2,4-dinitrofluorobenzene challenge, enzyme-linked immunosorbent assay and immunohistochemistry were used to measure the levels of IgE, interleukin 4 (IL-4), interferon-γ (IFN-γ), and histamine as well as the positive expression rate of SELE, respectively. The siRNA- SELE vector was constructed and transfection efficiency was estimated prior to performing quantitative reverse-transcription polymerase chain reaction and Western blot assay to determine the relative expression of SELE, eosinophil cationic protein (ECP), intercellular adhesion molecule 1 (ICAM-1), L-selectin (CD62L), and the alpha chain of leukocyte function-associated antigen-1 (CD11a). Adhesion assay was then performed to assess the cell adhesion ability in VECs. Elevated levels of IgE, IL-4, IFN-γ, and histamine and increased positive expression rate of SELE were indicative of successful establishment of mouse models of ICU. Furthermore, the relative expression levels of SELE, ECP, ICAM-1, CD62L, and CD11a were highest in the OE- SELE group. Besides, cell adhesion ability of VECs was notably promoted. Collectively, the current study define the potential role of SELE silencing as an inhibitor to ICU development by inhibiting cell adhesion ability of VECs.
Assuntos
Adesão Celular/efeitos dos fármacos , Selectina E/genética , Células Endoteliais/metabolismo , Terapia Genética/métodos , Molécula 1 de Adesão Intercelular/metabolismo , Interferência de RNA , Urticária/terapia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Selectina E/metabolismo , Endotélio Vascular/patologia , Feminino , Histamina/metabolismo , Humanos , Imunoglobulina E/metabolismo , Interferon gama/metabolismo , Interleucina-4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , RNA Interferente Pequeno/genética , Urticária/induzido quimicamenteRESUMO
BACKGROUND: This study aimed to explore the correlation of circulating inflammatory cytokines' levels with treatment response to etanercept (ETN) treatment in psoriasis patients. METHODS: 97 moderate-to-severe plaque-psoriasis patients were continuously recruited in this prospective cohort study, and all patients received ETN treatment. Serum samples were collected before and at 6 months (M6) after treatment, and nine inflammatory cytokines expressions were detected by enzyme-linked immuno sorbent assay. Psoriasis Area and Severity Index (PASI) score was evaluated at baseline (M0), 1 month (M1), 3 months (M3) and M6 after treatment, and the corresponding PASI 75/90 responses' rates were calculated. RESULTS: Tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6, IL-12, IL-17A, IL-22, IL-23, and IL-32 levels were reduced, while IL-10 level was elevated at M6 after ETN treatment compared to baseline. PASI 75/90 responses' rates to ETN were 69.1 and 38.1% at M6, respectively. IL-1ß and IL-17A levels were elevated in PASI 75-response patients compared to PASI 75 non-response patients, while IL-17A level was also increased in PASI 90-response patients compared to PASI 90 non-response patients. Multivariate logistic regression revealed that IL-1ß, IL-17A and combined phototherapy during study predicted higher, while previous systemic biologic treatment predicted lower PASI 75 response to ETN independently. In addition, IL-17A independently predicted higher PASI 90 response to ETN as well. CONCLUSIONS: IL-1ß, IL-17A, and combined phototherapy predicts higher while previous systemic biologic treatment predicts lower treatment response to ETN independently in psoriasis patients.
Assuntos
Etanercepte/uso terapêutico , Interleucina-17/metabolismo , Interleucina-1beta/metabolismo , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fototerapia/métodos , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Long noncoding RNA (lncRNA) colon cancer-associated transcript 2 (CCAT2) has been demonstrated to play an important role in diverse tumorigenesis. However, the biological function of lncRNAs in glioma is still unknown. In this study, we found that lncRNA CCAT2 was overexpressed in glioma tissues and cell lines and associated with tumor grade and size. Furthermore, patients with high levels of lncRNA CCAT2 had poorer survival than those with lower levels of lncRNA CCAT2. Knocking down lncRNA CCAT2 expression significantly suppressed the glioma cell growth, migration, and invasion, as well as induced early apoptosis of glioma cells in vitro. Moreover, lncRNA CCAT2 regulated epithelial-mesenchymal transition (EMT)-associated gene expression. In conclusion, lncRNA CCAT2 plays an important role in glioma tumorigenesis and progression and may act as a potential biomarker for therapeutic strategy and prognostic prediction.