RESUMEN
MicroRNAs (miRNAs) play an important role in the tumorigenesis of ovarian cancer. Previously, we have reported the dysregulation of miR-203 in the ovarian cancer tissues. However, the biological functions and molecular mechanisms of miR-203 in ovarian cancer remain unknown. Here, we showed that the expression of miR-203 was increased in ovarian cancer tissues compared with the adjacent non-cancerous tissues and the transcription of miR-203 was inhibited by P53. Forced expression of miR-203 in ovarian cancer promoted cell growth and migration, while depletion of miR-203 inhibited the growth and migration of ovarian cancer cells. In addition, miR-203 promoted the metastasis of ovarian cancer cells in vivo and shorted the survival of the nude mice. Mechanically, miR-203 targeted the 3'-UTR of pyruvate dehydrogenase B (PDHB) and increased the consumption of glucose and the production of lactate. Overexpression of PDHB abolished the oncogenic effects of miR-203 on the growth of ovarian cancer cells. Together, our data suggested the oncogenic roles of miR-203 in ovarian cancer by promoting glycolysis, and miR-203 might be a therapeutic target for ovarian cancer.
Asunto(s)
Movimiento Celular/genética , Proliferación Celular/genética , Glucólisis/genética , MicroARNs/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Complejo Piruvato Deshidrogenasa/metabolismo , Regiones no Traducidas 3'/genética , Animales , Carcinogénesis/genética , Línea Celular Tumoral , Femenino , Glucosa/metabolismo , Células HEK293 , Humanos , Ácido Láctico/biosíntesis , Ratones , Ratones Desnudos , MicroARNs/biosíntesis , Invasividad Neoplásica/genética , Metástasis de la Neoplasia/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
To clarify the influence of HIV on the intestinal flora and the interrelationship with CD4 T cells, the present study collected stool specimens from 33 HIV patients and 28 healthy subjects to compare the differences in the intestinal flora and CD4 T cells in a 16S rDNA-sequencing approach. ELISA was used to detect the expressions of interleukin 2 (IL-2), IL-8, and tumor necrosis factor-α (TNF-α). Meanwhile, correlation analysis with the different bacterial populations in each group was carried out. The results revealed that Alpha diversity indices of the intestinal flora of HIV patients were markedly lower than that of the healthy group (p < 0.05). The top five bacterial species in the HIV group were Bacteroides (23.453%), Prevotella (19.237%), Fusobacterium (12.408%), Lachnospira (3.811%), and Escherichia-Shigella (3.126%). Spearman correlation analysis results indicated that Fusobacterium_mortiferum, Fusobacterium, and Gammaproteobacteria were positively correlated with TNF-α (p < 0.05), whereas Ruminococcaceae, Bacteroidales was negatively correlated with TNF-α (p < 0.05). Additionally, Agathobacter was positively correlated with contents of IL-2 and IL-8 (p < 0.05), whereas Prevotellaceae, and Prevotella were negatively correlated with IL-8 content (p < 0.05). Furthermore, the top five strains in the CD4 high group (≥350/mm3) included Bacteroides (23.286%), Prevotella (21.943%), Fusobacterium (10.479%), Lachnospira (4.465%), and un_f_Lachnospiraceae (2.786%). Taken together, the present study identified that Fusobacterium and Escherichia-Shigella were specific and highly abundant in the HIV group and a correlation between the different bacterial flora and the contents of IL-2, IL-8, and TNF-α was revealed.
Asunto(s)
ADN Bacteriano/genética , Microbioma Gastrointestinal/genética , Infecciones por VIH , ARN Ribosómico 16S/genética , Linfocitos T CD4-Positivos/inmunología , Estudios de Casos y Controles , Citocinas/análisis , ADN Bacteriano/clasificación , Heces/química , Heces/microbiología , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Infecciones por VIH/microbiología , Humanos , Análisis de Secuencia de ADNRESUMEN
Overcoming senescence is a feature of ovarian cancer cells; however, the mechanisms underlying senescence regulation in ovarian cancer cells remain largely unknown. In this study, we found that ITPKA was downregulated in ovarian cancer samples, and the lower expression correlated with poor survival. Overexpression of ITPKA inhibited the anchorage-independent growth of ovarian cancer cells and induced senescence. However, knockdown of ITPKA promoted the anchorage-independent growth of ovarian cancer cells and inhibited senescence. Mechanistically, ITPKA was found to interact with MDM2, which stabilized P53, an essential regulator of senescence. Moreover, ITPKA was negatively regulated by miR-203, a microRNA that has been previously reported to be upregulated in ovarian cancer. Taken together, the results of this study demonstrated the tumor suppressive roles of ITPKA in ovarian cancer and provided a good explanation for the oncogenic roles of miR-203.
Asunto(s)
Carcinogénesis/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , Neoplasias Ováricas/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Animales , Línea Celular Tumoral , Senescencia Celular/genética , Regulación hacia Abajo , Femenino , Células HEK293 , Humanos , Masculino , Ratones , Neoplasias Ováricas/patología , Ovario/patología , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
In this study, an animal model of early myocardial ischemia (EMI) was established by ligating the left anterior descending coronary artery of rats. The experimental animals were divided into five groups according to different intervals of MI (15, 30min, 1, 2, and 3h) and one control group. Tissues from the apex of the myocardium and the adjacent myocardium were taken for paraffin sections, followed by hematoxylin-eosin and streptavidin-biotin-peroxidase complex (SABC) staining. Results showed that the myoglobin (Mb) depletion and the fibrinogen (Fg) staining increase were detected in the 30min MI group. The wavy-like increasing extension of the size and the intensity of the Mb depletion and the Fg staining intensification from the subendocardial to the subepicardial cells were observed along with the prolongation of the ischemic period. Both changes had similar patterns and sensitivity, except Fg was less reliable than Mb as it is more easily contaminated by blood. After overcoming blood contamination, the SABC-Fg technique will provide a new method for the diagnosis of EMI.