RESUMEN
Evidence shows that long noncoding RNAs (lncRNAs) modulate mRNAs of multiple genes by post-transcriptional regulation. However, in esophageal squamous cell carcinoma, lncRNAs involvement in post-transcriptional regulation of mRNAs have been rarely reported. In this study, we investigated a novel mechanism of linc01305 promoting metastasis and proliferation of ESCC. The results for real-time quantitative reverse transcription PCR (qRT-PCR) and fluorescence in situ hybridization showed that linc01305 was highly expressed and predominantly located in cytoplasm of human esophageal cancer cells. Transwell and colony formation assays confirmed that linc01305 promoted migration and proliferation of esophageal cancer cells. RNA-seq, linc01305 pulldown, mass spectrometry, RNA immunoprecipitation and mRNA stability assays demonstrated that linc01305 stabilized mRNA of target gene HTR3A through interacting with IGF2BP2 and IGF2BP3. Taken together, our data unveils a novel mechanism in which cytoplasmic linc01305 stabilizes HTR3A mRNA through interacting with IGF2BP2 and IGF2BP3 and thereby promotes metastasis and proliferation of ESCC.
Asunto(s)
Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/secundario , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/genética , Proteínas de Unión al ARN/metabolismo , Receptores de Serotonina 5-HT3/química , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Humanos , Pronóstico , Proteínas de Unión al ARN/genética , Receptores de Serotonina 5-HT3/genética , Receptores de Serotonina 5-HT3/metabolismo , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
BACKGROUND: Several studies have demonstrated a correlation between esophageal cancer (EC) and perturbed urinary metabolomic profiles, but none has described the correlation between urine metabolite profiles and those of the tumor and adjacent esophageal mucosa in the same patient. AIM: To investigate how urinary metabolic phenotypes were linked to the changes in the biochemical landscape of esophageal tumors. METHODS: Nuclear magnetic resonance-based metabolomics were applied to esophageal tumor tissues and adjacent normal mucosal tissues alongside patient-matched urine samples. RESULTS: Analysis revealed that specific metabolite changes overlapped across both metrics, including glucose, glutamate, citrate, glycine, creatinine and taurine, indicating that the networks for metabolic pathway perturbations in EC, potentially involved in but not limited to disruption of fatty acid metabolism, glucose and glycolytic metabolism, tricarboxylic acid cycle and glutaminolysis. Additionally, changes in most urinary biomarkers correlated with changes in biomarker candidates in EC tissues, implying enhanced energy production for rapid cell proliferation. CONCLUSION: Overall, these associations provide evidence for distinct metabolic signatures and pathway disturbances between the tumor tissues and urine of EC patients, and changes in urinary metabolic signature could reflect reprogramming of the aforementioned metabolic pathways in EC tissues. Further investigation is needed to validate these initial findings using larger samples and to establish the underlying mechanism of EC progression.
Asunto(s)
Mucosa Esofágica/metabolismo , Neoplasias Esofágicas/metabolismo , Redes y Vías Metabólicas , Metabolómica/métodos , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/orina , Progresión de la Enfermedad , Mucosa Esofágica/patología , Mucosa Esofágica/cirugía , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/orina , Esofagectomía , Femenino , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Metaboloma , Persona de Mediana Edad , Periodo Preoperatorio , Microambiente Tumoral , Urinálisis/métodosRESUMEN
To investigate potential dosimetric benefits and treatment efficiency of dynamic conformal arc therapy (DCA), intensity modulated radiation therapy (IMRT), and double partial arcs Rapidarc (RA) techniques in the treatment of early-stage peripheral lung cancer using stereotactic body radiotherapy (SBRT) with flattening filter free (FFF) beams. Twenty early-stage peripheral lung cancer patients were selected. For each patient, DCA, IMRT and RA plans were created to meet Radiation Therapy Oncology Group (RTOG) 0915 objectives with 48 Gy covering 95% of the planning target volume (PTV) in 4 fractions. PTV coverage, organs at risk (OARs) doses, planning time, monitor units (MU) and treatment time were evaluated. RA was significantly better than DCA for PTV coverage. RA provided a lower V32Gy to chest wall and less V20Gy to lung over those of DCA and IMRT. For other OARs, there is no significant difference among all three techniques. DCA plans showed significantly less planning time, shorter treatment time and lower MU number than those of RA and IMRT. RA provides a superior dosimetric benefit to DCA and IMRT in the treatment of early-stage lung cancer using SBRT with FFF beams. Considering the MU number, planning time and treatment efficiency, DCA technique is an effective treatment strategy.