RESUMEN
In a variety of cancers, long non-coding RNAs (lncRNAs) were believed to play important roles. Nevertheless, H19's possible molecular mechanism related to miR-20b-5p has not yet been explored in endometrial cancer. Differential lncRNAs in endometrial cancer were identified based on microarray analysis (GSE23339). In this research, in the first place, H19 expression was detected to be increased but miR-20b-5p to be decreased in endometrial cancer tissues and cells. Besides, H19 expression displayed a negative relationship to miR-20b-5p expression in endometrial cancer tissues. According to gain- and loss-of-function experiments of H19, like a ceRNA, H19 elevated AXL level and HIF-1α expression so as to stimulate the migration, proliferation and EMT process of endometrial cancer. Additionally, the knockdown of H19 slowed down tumor growth, promoted apoptosis and upregulated miR-20b-5p expression but lowered the expressions of HIF-1α, PCNA and AXL in vivo. Furthermore, H19 was also verified to stimulate the activity of endometrial cancer with AXL inhibitor BGB324 in vitro and in vivo. To sum up, H19 accelerates the tumor formation of endometrial cancer through the miR-20b-5p/AXL/HIF-1α signaling pathway, thereby providing a novel target for diagnosing and treating endometrial cancer.
Asunto(s)
Neoplasias Endometriales/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , ARN Largo no Codificante/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Transducción de Señal/genética , Animales , Apoptosis/genética , Benzocicloheptenos/farmacología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Biología Computacional , Neoplasias Endometriales/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/genética , ARN Largo no Codificante/genética , ARN Interferente Pequeño , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/genética , Trasplante Heterólogo , Triazoles/farmacología , Tirosina Quinasa del Receptor AxlRESUMEN
To investigate the roles of plasma miR-21 in the pathogenic process of Type 2 diabetes (T2D) with diabetic retinopathy (DR). T2D patients included patients without DR (NDR) group, patients with non-proliferative/background DR (BDR) group and patients with proliferative DR (PDR) group. Healthy individuals served as control group. Fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c), triacylglycerol (TG), total cholesterol (TC), urine creatinine (Cr), fasting blood glucose (FBG), blood urea nitrogen (BUN), low-density lipoprotein cholesterol (LDL-C), fasting insulin (FINS) and plasma miR-21 expression were measured. Quantitative real-time PCR (qRT-PCR) was applied to detect miR-21 expression. Pearson analysis was used to conduct correlation analysis and receiver operating characteristic (ROC) curve was used to analyse the diagnostic value of miR-21 in T2D with DR. Compared with the control group, FBG and HbA1c increased in the NDR group; compared with the control and NDR groups, disease course, HbA1c, FPG levels and homoeostasis model assessment of insulin resistance (HOMA-IR) were increased in the BDR and PDR groups; and compared with the BDR group, disease course, HbA1c and FPG levels were higher in the PDR group. miR-21 expression was higher in the BDR group than the control group, and higher in the PDR group than the BDR group. miR-21 expression was positively related with disease course, HbA1C, FPG and HOMA-IR, and had diagnostic value for T2D with DR and PDR. The plasma miR-21 expression was increased in the development of T2D with DR and can be used as an indicator for the severity of T2D with DR.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Retinopatía Diabética/sangre , MicroARNs/sangre , Índice de Severidad de la Enfermedad , Adulto , Anciano , Biomarcadores/sangre , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/complicaciones , Retinopatía Diabética/etiología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Resistencia a la Insulina , Modelos Lineales , Masculino , Metaboloma/fisiología , Persona de Mediana EdadRESUMEN
BACKGROUND: The aim of this study was to investigate the roles of cytochrome P450 2C19 (CYP2C19) polymorphisms in primary open-angle glaucoma (POAG) susceptibility and individual responses to drug treatment. MATERIAL/METHODS: This case-control study consisted of 93 cases with POAG and 125 controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze CYP2C19 single-nucleotide polymorphisms (SNPs). After timolol treatment, patients were classified into side effect (SE) group and non-side effect (NSE) group. According to drug treatment responses, patients were divided into 3 groups: excellent group (Ex) (IOP ≥8 mm Hg); utility group (Ut) (5