RESUMEN
Prostate cancer is the most common malignant tumor of the urinary system. The mechanisms of the initiation and progression of prostate cancer have not been fully elucidated. Increasing evidence suggests that circular RNAs (circRNAs) are involved in cancer pathogenesis. In this study, we aimed to identify differentially expressed circRNAs in prostate cancer tissues and explored the role of circRNAs in the pathogenesis of prostate cancer. By screening a circRNA microarray assay, we found that circ_0088233 was upregulated in prostate cancer tissues compared to adjacent normal tissues, and this upregulation can be verified in 46 pairs of prostate cancer and adjacent normal tissues examined using quantitative reverse transcription-PCR. The level of circ_0088233 correlated with the TNM stage. Knockdown of circ_0088233 reduced cell proliferation, migration, invasion, and induced G1 phase arrest and apoptosis. In addition, miR-185-3p was identified as the downstream target of circ_0088233 using luciferase reporter assays and a biotinylated circ_0088233 probe pull-down assay. The miR-185-3p level showed a negative correlation with the circ_0088233 level in prostate cancer tissues. Overexpression of circ_0088233 blocked the effects of miR-185-3p on cell proliferation, migration, invasion, cell cycle, and apoptosis. In conclusion, circ_0088233 may function as an oncogene and play an oncogenic role by sponging hsa-miR-185-3p. This study increases the understanding of circRNAs in the progression of prostate cancer. These results implicate circ_0088233 as a potential therapeutic target for prostate cancer.
RESUMEN
Non-coding RNAs play an important role in the pathogenesis of prostate cancer (PC). This study aims to characterize the role of GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms in the pathogenesis of PC. Both INS allele of GAS5 rs145204276 and A allele of HOTAIR rs4759314 were identified to increase the survival of PC patients. And patients carrying DEL/DEL + AG genotypes tend to present higher levels of HMGB1, GAS5, HOTAIR and lower levels of miR-1284 and miR-22. In addition, the transcription activity of GAS5 promoter was increased by the deletion allele of rs145204276 polymorphism, while the G allele of rs4759314 polymorphism increased the transcription activity of HOTAIR promoter. GAS5 and HOTAIR could bind to miR-1284 and miR-22, respectively, while miR-1284 and miR-22 could bind to the 3'UTR of HMGB1. Compared with the control group, the expressions of miR-1284 or miR-22 were decreased with the presence of GAS5 or HOTAIR, and the expression of HMGB1 was the highest in the GAS5 + HOTAIR group. In summary, the findings of this study demonstrated that both GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms could affect the prognosis of PC by modulating the expression of HMGB1 via modulating the GAS5/miR-1284/HMGB1 and HOTAIR/miR-22/HMGB1 signalling pathways.
Asunto(s)
Proteína HMGB1 , MicroARNs , Proteínas de Neoplasias , Polimorfismo Genético , Neoplasias de la Próstata , ARN Largo no Codificante , ARN Neoplásico , Transducción de Señal/genética , Anciano , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Humanos , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Células PC-3 , Pronóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismoRESUMEN
In a previous study by the present authors, it was identified that the expression of engrailed-2 (EN2) gene was downregulated in clear cell renal cell carcinoma (cc-RCC). The aim of the present study was to determine whether aberrant methylation was the mechanism underlying the silencing of EN2 gene in cc-RCC. A total of forty paired cc-RCC tissues, four cc-RCC cell lines and one normal human proximal tubule epithelial cell line were evaluated for EN2 gene methylation status using methylation-specific polymerase chain reaction (PCR). Following treatment with 5-Aza-dc, reverse transcription-quantitative PCR and western blot analysis were performed to examine the expression of EN2. Furthermore, cell proliferation, apoptosis and invasion assays were conducted to analyze the inhibitory effects of EN2 re-expression in 786-O cells. The results of the present study demonstrated that hyper-methylation of EN2 was identified in 12/40 cc-RCC tissues and all cc-RCC cell lines. The methylation status of the EN2 gene was revealed to be associated with histological grade and tumor size in cc-RCC. Following 5-Aza-dc treatment, demethylation of the EN2 gene was identified in 786-O cells, in conjunction with EN2 re-expression. Furthermore, re-activation of the EN2 gene markedly inhibited the proliferative and invasive capacities of cc-RCC. The results of the present study demonstrated that the EN2 gene promoter was hyper-methylated in cc-RCC, which may underlie the silencing of the EN2 gene in cc-RCC.
RESUMEN
Our preliminary study indicated that Engrailed-2 (EN2) is downregulated but also ectopically expressed in clear-cell renal cell carcinoma (CCRCC), and the absence of EN2 expression was associated with poor histological grade. However, the specific roles of EN2 in CCRCC have yet to be elucidated. In the present study, we examined the effects of inhibiting EN2 expression by human renal tubular epithelial cells (HK-2) and overexpressing EN2 by human clear-cell renal cells (786-O). Results showed that EN2 inhibition accelerated HK-2 cell proliferation, shortened the cell cycle, reduced apoptosis, and acted more invasively. By contrast, EN2 overexpression in 786-O cells decelerated the proliferative ability of 786-O, increased the percentage of cell apoptosis, and weakened the invasive ability. Overall, the results demonstrated that EN2 might play an anti-oncogenic role in oncogenesis and development of CCRCC, thereby maintaining the normal growth of human renal tubular epithelial cells.
Asunto(s)
Carcinoma de Células Renales/metabolismo , Proteínas de Homeodominio/metabolismo , Neoplasias Renales/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Apoptosis/genética , Carcinoma de Células Renales/genética , Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Expresión Génica , Proteínas de Homeodominio/genética , Humanos , Neoplasias Renales/genética , Proteínas del Tejido Nervioso/genética , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
The aim of this study was to assess the diagnostic value of RASSF1A methylation in renal cell carcinoma. Systematically search were performed using the Pubmed, ProQest and Web of Science for all articles on the association between RASSF1A methylation and renal cell carcinoma before 15 April 2015. After the filtration, 13 studies involving 677 cases and 497 controls met our criteria. Our meta-analysis suggested that hypermethylation of RASSF1A gene was associated with the increased risk of RCC(OR:4.14, 95%CI:1.06-16.1). Stratified analyses showed a similar risk in qualitative detection method(OR:28.4, 95%CI:10.2-79.6), body fluid sample(OR:12.8, 95%CI:5.35-30.8), and American(OR:10.5, 95%CI:1.97-55.9). Our result identified that RASSF1A methylation had a strong potential in prediction the risk of Renal cell carcinoma.