RESUMEN
BACKGROUND: Long non-coding RNAs (lncRNAs) have been implicated as functional molecules in hepatocellular carcinoma (HCC) progression. The present research aimed to investigate the levels of LncRNA cancer susceptibility candidate gene 19 (CASC19) in HCC tissues and cell lines and to explore its potential role in the diagnosis and prognosis of HCC. METHODS: HCC tissues and cell lines were collected to assess the levels of CASC19 by real-time quantitative reverse transcription PCR (RT-qPCR). The prognostic value of CASC19 was evaluated using the Kaplan-Meier method and Cox regression analysis. The functional role of CASC19 in regulating HCC cell proliferation, migration, and invasion was evaluated by Cell Counting Kit-8 (CCK-8) and Transwell analysis. The potential targeted miR-140-5p of CASC19 was confirmed by a dual-luciferase reporter assay. RESULTS: High CASC19 expression positively correlated with tumor size, differentiation, and TNM stage in HCC patients (P < 0.05). Patients with high CASC19 expression have a poorer survival prognosis and are prone to relapse compared to those with low CASC19. miR-140-5p, a target miRNA for CASC19, negatively correlated with CASC19 levels in tumor tissues. Reduced CASC19 levels attenuated cell proliferation, migration, and invasion, but this attenuation was reversed by suppression of miR-140-5p. CONCLUSION: Up-regulated CASC19 may serve as a biomarker for predicting poor prognosis in HCC patients. In vitro, overexpressed CASC19 promoted the progression of HCC, indicating that CASC19 may be a possible therapeutic target for the treatment of HCC.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/metabolismo , Línea Celular Tumoral , Recurrencia Local de Neoplasia/genética , MicroARNs/genética , MicroARNs/metabolismo , Pronóstico , Proliferación Celular/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Movimiento Celular/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Purpose: To develop and validate a gene-related nomogram for predicting the risk of lymph node (LN) metastasis preoperatively in patients with colorectal cancer (CRC). Methods: RNA-seq data of 581 CRC and 51 normal cases with clinical features were downloaded from TCGA database. In the evaluation cohort with 381 CRC cases, the LASSO regression was used to reduce dimensionality of gene signatures extracted to build gene score. A gene-related nomogram was performed based on the multivariable logistic regression analysis. The performance of the nomogram was assessed by the discrimination, calibration, and clinical usefulness not only in the evaluation, but also in the validation cohort with 200 CRC cases. Results: A total of 12,590 differentially expressed genes were selected, in which 59 candidates associated with LN metastasis in differentially expressed genes set were screened by LASSO to form the gene score. Based on the analysis of multivariate logistic regression, the gene-related nomogram showed good calibration and discrimination not only in the evaluation cohort (concordance-index 0.93; 95%CI 0.91-0.96), but also in the validation cohort (concordance-index 0.70; 95%CI 0.63-0.78). The decision curve analysis of the gene-related nomogram also provides constructive guidance for the design of operation plan, preoperatively. Conclusions: The presented genes nomogram may predict the LN metastasis in CRC patients, preoperatively. And 59 hub genes were defined related to LN metastasis of CRC, which can serve as treatment targets for the further study. Preoperative biopsy and gene analysis are needed to develop the operation plan in clinical practice.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Colorrectales/cirugía , Metástasis Linfática/diagnóstico , Nomogramas , Planificación de Atención al Paciente , Adulto , Biopsia , Toma de Decisiones Clínicas/métodos , Estudios de Cohortes , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Conjuntos de Datos como Asunto , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/genética , Metástasis Linfática/patología , Metástasis Linfática/terapia , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , RNA-Seq , Curva ROC , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: The aim of this study was to prepare aclacinomycin A (ACM)-loaded solid lipid nanoparticles (SLNs) and to evaluate their in vitro and in vivo characteristics. METHODS: SLNs were prepared using an emulsion evaporation-solidification method, and characterized in accordance with the morphological examination, particle size distribution, entrapment efficiency, drug-loading, and in vitro release. Pharmacokinetic and biodistribution studies were employed to evaluate the in vivo of SLNs. RESULTS: The SLNs were spherical in shape, uniform in size, and appropriate for administration via intravenous injection. The drug content, encapsulation efficiency, and drug loading of prepared SLNs were 96.4% ± 4.6%, 86.7% ± 2.3%, and 4.8% ± 0.7% (n = 3), respectively, and the mean diameter was 68.2 ± 5.6 nm from three batches. The SLNs were produced with stable physical properties and demonstrated significantly sustained release. The pharmacokinetic behavior of ACM was greatly improved by lyophilized injection of SLN with sustained drug release and high bioavailability. In addition, the results obtained from tissue distribution showed that ACM-SLNs were hepatic targeting in vivo. CONCLUSIONS: The present work demonstrated the feasibility of liver-targeted delivery of ACM utilizing SLNs.