RESUMEN
BACKGROUND: The human death-associated protein 3 (hDAP3) is a GTP-binding constituent of the small subunit of the mitochondrial ribosome with a pro-apoptotic function. METHODS: A search through publicly available microarray data sets showed 337 genes potentially coregulated with the DAP3 gene. The promoter sequences of these 337 genes and 70 out of 85 mitochondrial ribosome genes were analysed in silico with the DAP3 gene promoter sequence. The mitochondrial role of DAP3 was also investigated in the thyroid tumours presenting various mitochondrial contents. RESULTS: The study revealed nine transcription factors presenting enriched motifs for these gene promoters, five of which are implicated in cellular growth (ELK1, ELK4, RUNX1, HOX11-CTF1, TAL1-ternary complex factor 3) and four in mitochondrial biogenesis (nuclear respiratory factor-1 (NRF-1), GABPA, PPARG-RXRA and estrogen-related receptor alpha (ESRRA)). An independent microarray data set showed the overexpression of ELK1, RUNX1 and ESRRA in the thyroid oncocytic tumours. Exploring the thyroid tumours, we found that DAP3 mRNA and protein expression is upregulated in tumours presenting a mitochondrial biogenesis compared with the normal tissue. ELK1 and ESRRA were also showed upregulated with DAP3. CONCLUSION: ELK1 and ESRRA may be considered as potential regulators of the DAP3 gene expression. DAP3 may participate in mitochondrial maintenance and play a role in the balance between mitochondrial homoeostasis and tumourigenesis.
Asunto(s)
Adenoma Oxifílico/genética , Adenoma Oxifílico/metabolismo , Proteínas Reguladoras de la Apoptosis/biosíntesis , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Ribosómicas/biosíntesis , Proteínas Ribosómicas/genética , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Reparación de la Incompatibilidad de ADN , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Mitocondrias/genética , Mitocondrias/metabolismo , Regiones Promotoras Genéticas , Biosíntesis de Proteínas , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Proteínas de Unión al ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ribosomas/genética , Factores de Transcripción/genéticaRESUMEN
Out of 163 STEMI patients, 33 presented left ventricular remodeling (LVR) as assessed by multiple cardiac magnetic resonance (CMR) scans. LVR patients were identified as EarlyLVR (LVR occurring between baseline and 3â¯months) or LateLVR (LVR occurring between 3â¯months and one year), and matched to non-remodeler patients in term of age, gender, anterior infarction, baseline LV ejection fraction and infarct size. ST2 and NT-proBNP were measured at baseline and 3â¯months. Systolic wall stress (SWS) was calculated by CMR. At baseline, mean levels of ST2, NT-proBNP and SWS were 67.1⯱â¯54.1â¯ng/mL, 1529⯱â¯1702â¯ng/L and 17.9⯱â¯7.1 103â¯N·m-2, respectively, and did not differ among the groups. At 3â¯months, EarlyLVR patients presented significant higher ST2, NT-proBNP and SWS (31.6⯱â¯12.7â¯ng/mL, 1142⯱â¯1069â¯ng/L, 25.5⯱â¯9.7 103â¯N·m-2), compared to the corresponding non-remodelers (20.5⯱â¯8.6â¯ng/mL, 397⯱â¯273â¯ng/L, 18⯱â¯7.3 103â¯N·m-2; with pâ¯=â¯0.017, 0.040, and 0.036, respectively). LateLVR patients presented higher ST2 at 3â¯months than their non-remodelers (33.6⯱â¯15.9 versus 23.66⯱â¯8.7â¯ng/mL, pâ¯=â¯0.046), while NT-proBNP and SWS were not different between groups at both timepoints.
Asunto(s)
Proteína 1 Similar al Receptor de Interleucina-1/sangre , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Remodelación Ventricular/fisiología , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de TiempoRESUMEN
Conventional histology failed to classify part of non-medullary thyroid lesions as either benign or malignant. The group of tumours of uncertain malignancy (T-UM) concerns either atypical follicular adenomas or the recently called 'tumours of uncertain malignant potential'. To refine this classification we analysed microarray data from 93 follicular thyroid tumours: 10 T-UM, 3 follicular carcinomas, 13 papillary thyroid carcinomas and 67 follicular adenomas, compared to 73 control thyroid tissue samples. The diagnosis potential of 16 selected genes was validated by real-time quantitative RT-PCR on 6 additional T-UM. The gene expression profiles in several groups were examined with reference to the mutational status of the RET/PTC, BRAF and RAS genes. A pathological score (histological and immunohistochemical) was estimate for each of the T-UM involved in the study. The correlation between the T-UM gene profiles and the pathological score allowed a separation of the samples in two groups of benign or malignant tumours. Our analysis confirms the heterogeneity of T-UM and highlighted the molecular similarities between some cases and true carcinomas. We demonstrated the ability of few marker genes to serve as diagnosis tools and the need of a T-UM pathological scoring.