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An amendment to this paper has been published and can be accessed via the original article.
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BACKGROUND: Circular RNAs (circRNAs) have been found to play critical roles in the development and progression of various cancers. However, little is known about the effects of the circular RNA network on glioblastoma multiforme (GBM). METHODS: A microarray was used to screen circRNA expression in GBM. Quantitative real-time PCR was used to detect the expression of circMMP9. GBM cells were transfected with a circMMP9 overexpression vector or siRNA, and cell proliferation, migration and invasion, as well as tumorigenesis in nude mice, were assessed to examine the effect of circMMP9 in GBM. Biotin-coupled miRNA capture, fluorescence in situ hybridization and luciferase reporter assays were conducted to confirm the relationship between circMMP9 and miR-124. RESULTS: In this study, we screened differentially expressed circRNAs and identified circMMP9 in GBM. We found that circMMP9 acted as an oncogene, was upregulated in GBM and promoted the proliferation, migration and invasion abilities of GBM cells. Next, we verified that circMMP9 served as a sponge that directly targeted miR-124; circMMP9 accelerated GBM cell proliferation, migration and invasion by targeting miR-124. Furthermore, we found that cyclin-dependent kinase 4 (CDK4) and aurora kinase A (AURKA) were involved in circMMP9/miR-124 axis-induced GBM tumorigenesis. Finally, we found that eukaryotic initiation factor 4A3 (eIF4A3), which binds to the MMP9 mRNA transcript, induced circMMP9 cyclization and increased circMMP9 expression in GBM. CONCLUSIONS: Our findings indicate that eIF4A3-induced circMMP9 is an important underlying mechanism in GBM cell proliferation, invasion and metastasis through modulation of the miR-124 signaling pathway, which could provide pivotal potential therapeutic targets for the treatment of GBM.
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Neoplasias Encefálicas/genética , Carcinogénesis/genética , ARN Helicasas DEAD-box/genética , Factor 4A Eucariótico de Iniciación/genética , Glioblastoma/genética , Metaloproteinasa 9 de la Matriz/genética , MicroARNs/genética , ARN/genética , Animales , Aurora Quinasa A/genética , Neoplasias Encefálicas/patología , Carcinogénesis/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , ARN Helicasas DEAD-box/metabolismo , Factor 4A Eucariótico de Iniciación/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patología , Xenoinjertos , Humanos , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Desnudos , MicroARNs/metabolismo , ARN/biosíntesis , ARN Circular , Regulación hacia ArribaRESUMEN
Circular RNA and long noncoding RNA function as efficient miRNA sponges that regulate gene expression in eukaryotes. However, the sponges of functional miRNAs in glioblastoma remain largely unknown. Here, we identify a subset of circRNAs and lncRNAs that are specifically increased in miR-422a-downregulated glioblastoma tissues. We characterized a novel circRNA derived from NT5E, named circNT5E, that is regulated by ADARB2 binding to sites flanking circRNA-forming introns. We hypothesized that circNT5E may serve as a sponge against miR-422a in glioblastoma tumorigenesis. circNT5E controlled multiple pathologic processes, including cell proliferation, migration, and invasion. circNT5E directly bound miR-422a and inhibited miR-422a activity. Furthermore, circNT5E was observed to sponge other miRNAs, exhibiting tumor suppressor-like features in glioblastoma. Taken together, these findings highlight a novel oncogenic function of circRNA in glioblastoma tumorigenesis.Significance: Microarray profiling of circRNA/lncRNA/mRNA in glioblastoma identifies circNT5E as an oncogenic circular RNA and a sponge of miR-422a. Cancer Res; 78(17); 4812-25. ©2018 AACR.
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Carcinogénesis/genética , Glioblastoma/genética , MicroARNs/genética , ARN/genética , Adenosina Desaminasa/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Glioblastoma/patología , Humanos , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Unión Proteica/genética , ARN Circular , Proteínas de Unión al ARN/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
The purpose of this study was to explore the role of neuropeptide Y (NPY) on molecular and histological changes in human pituitary adenomas. The localization of NPY and its expression at the protein, messenger RNA (mRNA), and receptor levels were investigated here in different subcategories of pituitary adenomas. Immunohistochemical staining was performed in all cases to assess expression of NPY. Reverse transcription-polymerase chain reaction (RT-PCR) was used to study the mRNA expression of NPY. NPY subcellular localization was observed using immunoelectron microscopy in cytoplasm, rough endoplasmic reticulum, and cell matrix in four of the six cases of pituitary adenoma. NPY protein expression was observed in 59.6% of 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. mRNA expression of NPY was observed in all 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. Significantly different levels of expression were observed across different subcategories of pituitary adenoma. mRNA expression of Y1R and Y2R was observed across all subcategories of pituitary adenomas, and a positive correlation was observed between NPY and Y2R. In conclusion, evidence is provided here for the expression of NPY and its receptors, Y1R and Y2R, in human pituitary adenoma, and the levels of expression were found to differ across different subcategories. Differences in expression of Y2R in human pituitary adenomas were found to have remarkable statistical significance.
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Adenoma/patología , Neuropéptido Y/análisis , Neuropéptido Y/genética , Hipófisis/patología , Neoplasias Hipofisarias/patología , ARN Mensajero/análisis , Adenoma Hipofisario Secretor de ACTH/química , Adenoma Hipofisario Secretor de ACTH/genética , Adenoma Hipofisario Secretor de ACTH/patología , Adenoma/química , Adenoma/genética , Adolescente , Adulto , Anciano , Citoplasma/química , Retículo Endoplásmico Rugoso/química , Femenino , Adenoma Hipofisario Secretor de Hormona del Crecimiento/química , Adenoma Hipofisario Secretor de Hormona del Crecimiento/genética , Adenoma Hipofisario Secretor de Hormona del Crecimiento/patología , Humanos , Hiperplasia/genética , Hiperplasia/metabolismo , Inmunohistoquímica , Masculino , Microscopía Inmunoelectrónica , Persona de Mediana Edad , Hipófisis/química , Neoplasias Hipofisarias/química , Neoplasias Hipofisarias/genética , Prolactinoma/química , Prolactinoma/genética , Prolactinoma/patología , Receptores de Neuropéptido Y/genética , Adulto JovenRESUMEN
BACKGROUND: Fungal infections of the central nervous system, especially cerebral mucormycosis or brain abscess are very rare.Cerebral mucormycosis is a rare disease. It is not an independent disease, but a secondary opportunistic infectious disease. MATERIALS AND METHODS: This study has collected the data of 81 cases of intracranial mucormycosis from 28 Chinese hospitals, within 37 years, as well as reviewed the literatures and retrospectively analyzed and summarized this disease's background, clinical classifications, risk factors, pathology, clinical manifestations, diagnosis, treatment, and prognosis. RESULTS: The 81 IM cases were aged between 15 days (the youngest) and 79 years (oldest), with a mean age of 41.6 years. Among them, 12 cases were <1 year old (the infant group), six cases were within one to 13 years old (the children group), and 63 cases were >14 years old (the adult group ). 45 cases were male and 36 were female, with a male/female ratio of 1.25:1.0. The shortest duration of the disease was three days, and the longest was 248 days. CONCLUSIONS: This study helped to realize an early diagnosis and treatment, improve the cure rate, and reduce mortality.
