ABSTRACT
OBJECTIVE@#To explore the effect of HNF1A-AS1 on the proliferation, migration and invasion of IL-6-induced hemangioendothelial cells (HemEC) and possible mechanism.@*METHODS@#RT-qPCR was used to detect the expression level of HNF1A-AS1 and miR-363-3p in the tumor tissue and adjacent normal skin tissue from 35 patients with hemangioma. Pearson correlation was used to analyze the correlation between the expression of HNF1A-AS1 and miR-363-3p in tumor tissues. HemEC were isolated and cultured in vitro.Dual luciferase reporter gene experiment was used to study the regulatory effect between HNF1A-AS1 and miR-363-3p. IL-6 was added to HemEC transfected with si-NC, si-HNF1A-AS1, si-HNF1A-AS1 and anti-miR-NC, or si-HNF1A-AS1 and anti-miR-363-3p, respectively. CCK-8 method and clone formation experiment were used to detect cell proliferation in each group. Transwell method was used to detect cell migration and invasion in each group. Western blotting was used to detect the expression of Ki67, MMP-2 and MMP-9 proteins in each group.@*RESULTS@#Compared with normal skin tissues, the expression of IL-6 mRNA in hemangioma tissues was increased (P<0.05), and the expression of IL-6 mRNA in the proliferative phase was lower than that in the degenerative phase (P<0.05). Expression of HNF1A-AS1 in hemangioma tissue was increased (P<0.05), while that of miR-363-3p was decreased (P<0.05), and the two were negatively correlated (r=-0.758, P<0.05). HNF1A-AS1 down-regulated the expression of miR-363-3p in HemEC.IL-6 promoted the expression of HNF1A-AS1, OD value, number of colonies, number of migration and invasion of HemEC cells, and the expression of Ki67, MMP-2 and MMP-9proteins (P<0.05), while reduced the expression of miR-363-3p (P<0.05). Down-regulating si-HNF1A-AS1 reduced the IL-6-induced HemEC cell OD value, colony numbers, migration and invasion and the expression of Ki67, MMP-2 and MMP-9 proteins (P<0.05). Down-regulating miR-363-3p attenuated the inhibitory effect of down-regulating si-HNF1A-AS1 on the proliferation, migration and invasion of HemEC cells induced by IL-6 (P<0.05).@*CONCLUSION@#Expression of HNF1A-AS1 is increased in hemangioma tissues. Down-regulating HNF1A-AS1 may inhibit proliferation, migration and invasion of IL-6-induced hemangioma endothelial cells by targeted up-regulation of miR-363-3p.
Subject(s)
Humans , Cell Line, Tumor , Cell Movement , Cell Proliferation , Endothelial Cells , Gene Expression Regulation, Neoplastic , Hemangioma/genetics , Hepatocyte Nuclear Factor 1-alpha/genetics , Interleukin-6/genetics , MicroRNAs/genetics , RNA, Long NoncodingABSTRACT
El síndrome de Sturge-Weber consiste, en su forma completa, en la asociación de anomalías cerebrales, cutáneas y oculares. Desde el punto de vista clínico, se caracteriza por una mancha color vino en la cara, epilepsia, retraso mental, otras manifestaciones neurológicas deficitarias y glaucoma. Se presentó el caso de un paciente de 9 años de edad, masculino, piel negra, producto de parto eutócico, con peso de 4 200 g y antecedentes patológicos perinatales de cianosis, constatándose desde el nacimiento varios hemangiomas faciales. Al examen físico se confirma en cara y cráneo, una frente huidiza con presencia del hemangioma facial o hemangioma coroideo, glaucoma unilateral izquierdo, micrognatia. Se precisó mala oclusión dentaria, y en las extremidades superiores una clinodactilia del quinto dedo. Además, tiene el tronco asimétrico, retraso mental severo y aparecen cuadros convulsivos tónico-clónicos que repiten frecuentemente. Teniendo en cuenta todos estos elementos se comienza a sospechar el posible diagnóstico de un síndrome de Sturge-Weber (AU).
The Sturge-Weber syndrome is, in its complete form, the association of ocular, cutaneous and cerebral anomalies. From the clinical point of view, it is characterized by a wine-color spot on the face, epilepsy, mental retardation, other neurological deficit manifestations and glaucoma. We presented the case of a male, black patient, aged 9 years, who was born by eutocic delivery, with 4 200 g weight, and perinatal symptoms of cyanosis, finding several facial hemangioma from the moment of birth. At the physical examination, it was confirmed on the face and crania, evasive forehead with facial hemangioma or choroidal hemangioma, left unilateral glaucoma, micrognathia. Dental malocclusion was stated and clinodactyly of the fifth finger. Besides that, he has an asymmetric trunk, severe mental retardation and tonic-clonic convulsive episodes frequently repeated. Taking into account all these elements we began to suspect the possible diagnosis of a Sturge-Weber syndrome (AU).
Subject(s)
Humans , Male , Female , Child , Sturge-Weber Syndrome/epidemiology , Hemangioma/epidemiology , Sturge-Weber Syndrome/complications , Sturge-Weber Syndrome/diagnosis , Sturge-Weber Syndrome/genetics , Sturge-Weber Syndrome/pathology , Hemangioma/genetics , Hemangioma/pathology , Neurologic ManifestationsABSTRACT
El síndrome de Beckwith-Wiedemann (SBW) es un desorden esporádico o heredado, infrecuente, que se caracteriza por peso elevado al nacimiento, macroglosia, defectos de la pared abdominal y menos frecuentemente hipoglucemia, hemihipertrofia y visceromegalia. Se presenta un paciente de sexo femenino de un mes de vida con antecedentes de nefromegalia evidenciada por ecografía prenatal con múltiples hemangiomas en tronco y labio superior. Al examen físico se evidenció notable macroglosia, hemihipertrofia con compromiso de genitales externos, onfalocele y percentilo de peso mayor a 90. El laboratorio demostró alfa fetoproteína de 608ng/ml. Se realizó diagnóstico de síndrome de Beckwith Wiedemann. El paciente evolucionó con aumento del número y tamaño de las lesiones hemangiomatosas, descenso de los niveles de alfa fetoproteína y su maduración psicomotriz fue adecuada a su edad. Presentamos un síndrome infrecuente en un paciente con hemangiomatosis neonatal benigna (HNB), asociación no descripta previamente en la literatura. Destacamos la importancia del examen físico en la consulta dermatológica como oportunidad diagnóstica.
Beckwith-Wiedemanns syndrome is a sporadic or hereditary rare disor-der characterized by macroglosia, omphalocele, visceromegalia, hypo-glycemia and hemihypertrophy.We report the case of a 1 month-old infant with a history of nephromegalia detected by prenatal ultrasound scan, who presented various generalized hemangiomas.On examination she had macroglosia, hemihypertrophy, omphalocele and high body weight. She also had alpha feto protein 608 ng/ml withno further abnormalities, leading us to diagnose Beckwith-Wiedemann ́s syndrome.The interest of this case is to report an infrecuent syndrome in a patient with diagnosis of neonatal hemangiomatosis. This association has not been previously reported in the literature. We wish to emphasize the importance of a thorough physical exam as part of the dermatologic consultation leading to the correct diagnosis.
Subject(s)
Humans , Female , Infant , Beckwith-Wiedemann Syndrome/diagnosis , Beckwith-Wiedemann Syndrome/genetics , Urogenital Abnormalities/genetics , Skin Diseases/pathology , Hyperplasia , Hemangioma/genetics , Macroglossia , Practice Guidelines as Topic , alpha-Fetoproteins/analysisABSTRACT
As iodotironinas desiodases formam uma família de selenoenzimas com propriedades catalíticas distintas que ativam ou inativam os hormônios tireoidianos via desiodação do anel fenólico ou tirosínico da molécula do T4. As desiodases tipo I e II (D1 e D2) são as enzimas responsáveis pela geração do T3 e são amplamente expressas na tireóide normal. A transformação neoplásica benigna ou maligna da glândula tireóide está associada a alterações na expressão dessas isoenzimas, sugerindo um possível papel da D1 e da D2 como marcadores de diferenciação celular. Anormalidades na expressão de ambas enzimas e da desiodase tipo III (D3), inativadora do hormônios tireoidianos, são também encontradas em outras neoplasias humanas. Os mecanismos ou implicações do aumento ou diminuição das desiodases na patogênese neoplásica são pouco compreendidas. No entanto, é importante observar que a expressão anormal da D2 pode ser responsável por um quadro de tireotoxicose em pacientes com metástases de carcinoma folicular de tireóide, enquanto que o aumento da D3 em hemangiomas pode causar hipotireoidismo de difícil tratamento.
The iodothyronine deiodinases constitute a family of selenoenzymes that catalyze the removal of iodine from the outer ring or inner ring of the thyroid hormones. The activating enzymes, deiodinases type I (D1) and type II (D2), are highly expressed in normal thyroid gland. Benign or malignant neoplastic transformation of the thyroid cells is associated with changes on the expression of these enzymes, suggesting that D1 or D2 can be markers of cellular differentiation. Abnormalities on the expression of both enzymes and also of the deiodinase type III (D3), that inactivates thyroid hormones, have been found in other human neoplasias. So far, the mechanism or implications of these findings on tumor pathogenesis are not well understood. Nevertheless, its noteworthy that abnormal expression of D2 can cause thyrotoxicosis in patients with metastasis of follicular thyroid carcinoma and that increased D3 expression in large hemangiomas causes severe hypothyroidism.