RESUMO
The frequently encountered wastewater contaminations, including soluble aromatic compound and dye pollutants, pathogenic bacteria, and insoluble oils, have resulted in significant environmental and human health issues. It poses a challenge to utilize identical materials for the treatment of complex wastewater. Herein, in this research, multifunctional Ag NPs/guar gum hybrid hydrogels were fabricated using a facile in situ reduction and self-crosslinking method for efficient remediation of complex wastewater. The Ag NPs/guar gum hybrid hydrogel showed remarkable remodeling, adhesive, and self-healing characteristics, which was favorable for its versatile applications. The combination of Ag NPs with the guar gum skeleton endowed the hybrid hydrogel with exceptional catalytic activity for reducing aromatic compounds and dye pollutants, as well as remarkable antibacterial efficacy against pathogenic bacteria. In addition, the Ag NPs/guar gum hybrid hydrogel could be employed to coat a variety of substrates, including cotton fabrics and stainless steel meshes. The hydrogel coated cotton fabrics and meshes presented superhydrophilicity/underwater superoleophobicity, excellent antifouling capacity, and outstanding recyclability, which could be successfully applied for efficient separation of oil-water mixtures. The findings of this work provide a feasible and cost-effective approach for the remediation of intricate wastewater.
Assuntos
Antibacterianos , Galactanos , Hidrogéis , Mananas , Nanopartículas Metálicas , Gomas Vegetais , Prata , Galactanos/química , Gomas Vegetais/química , Prata/química , Mananas/química , Antibacterianos/química , Antibacterianos/farmacologia , Catálise , Nanopartículas Metálicas/química , Hidrogéis/química , Águas Residuárias/química , Purificação da Água/métodos , Água/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Óleos/químicaRESUMO
Intracranial dissemination is rare among patients with glioblastoma multiforme (GBM). Very few GBM patients develop symptoms from intracranial dissemination, as most do not surviving long enough for intracranial dissemination to become clinically evident. Herein, we report a case of GBM in a 39-year-old woman who underwent surgical resection, concomitant chemoradiotherapy, and seven courses of adjuvant chemotherapy with temozolomide. The patient then complained of an instable gait and hearing loss. Imaging studies demonstrated that although the primary intracranial tumors were well-controlled by treatment, contralateral cerebellopontine angle seeding dissemination was present. The patient died 3 months after the diagnosis of seeding dissemination. In light of a previous report and our current case, heightened awareness could promote surgical strategies that minimize the possibility of dissemination, including avoiding ventricular entry or a no-touch strategy.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Adulto , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Quimiorradioterapia/métodos , Quimioterapia Adjuvante , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Temozolomida/uso terapêuticoRESUMO
Resection of brain tumors frequently causes injury to the surrounding brain tissue that exacerbates cerebral edema by activating an inflammatory cascade. Although corticosteroids are often utilized peri-operatively to alleviate the symptoms associated with brain edema, they increase operative morbidities and suppress the efficacy of immunotherapy. Thus, novel approaches to minimize cerebral edema caused by neurosurgical procedures will have significant utility in the management of patients with brain tumors. We have studied the role of the receptor for advanced glycation end products (RAGE) and its ligands on inflammatory responses to neurosurgical injury in mice and humans. Blood-brain barrier (BBB) integrity and neuroinflammation were characterized by Nanostring, flow cytometry, qPCR, and immunoblotting of WT and RAGE knockout mice brains subjected to surgical brain injury (SBI). Human tumor tissue and fluid collected from the resection cavity of patients undergoing craniotomy were also analyzed by single-cell RNA sequencing and ELISA. Genetic ablation of RAGE significantly abrogated neuroinflammation and BBB disruption in the murine SBI model. The inflammatory responses to SBI were associated with infiltration of S100A9-expressing myeloid-derived cells into the brain. Local release of pro-inflammatory S100A9 was confirmed in patients following tumor resection. RAGE and S100A9 inhibitors were as effective as dexamethasone in attenuating neuroinflammation. However, unlike dexamethasone and S100A9 inhibitor, RAGE inhibition did not diminish the efficacy of anti-PD-1 immunotherapy in glioma-bearing mice. These observations confirm the role of the RAGE axis in surgically induced neuroinflammation and provide an alternative therapeutic option to dexamethasone in managing post-operative cerebral edema.
Assuntos
Anti-Inflamatórios , Edema Encefálico , Neoplasias Encefálicas , Receptor para Produtos Finais de Glicação Avançada , Animais , Anti-Inflamatórios/farmacologia , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Lesões Encefálicas/complicações , Neoplasias Encefálicas/cirurgia , Dexametasona/uso terapêutico , Modelos Animais de Doenças , Humanos , Camundongos , Ratos , Ratos Sprague-Dawley , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidoresRESUMO
BACKGROUND: Increased expression of the transcription factor Forkhead box M1 (FOXM1) has been reported to play an important role in the progression and development of multiple tumors, but the molecular mechanisms that regulate FOXM1 expression remain unknown, and the role of FOXM1 in aerobic glycolysis is still not clear. METHODS: The expression of FOXM1 and NADPH oxidase 4 (NOX4) in normal brain tissues and glioma was detected in data from the TCGA database and in our specimens. The effect of NOX4 on the expression of FOXM1 was determined by Western blot, qPCR, reactive oxygen species (ROS) production assays, and luciferase assays. The functions of NOX4 and FOXM1 in aerobic glycolysis in glioblastoma cells were determined by a series of experiments, such as Western blot, extracellular acidification rate (ECAR), lactate production, and intracellular ATP level assays. A xenograft mouse model was established to test our findings in vivo. RESULTS: The expression of FOXM1 and NOX4 was increased in glioma specimens compared with normal brain tissues and correlated with poor clinical outcomes. Aberrant mitochondrial reactive oxygen species (ROS) generation of NOX4 induced FOXM1 expression. Mechanistic studies demonstrated that NOX4-derived MitoROS exert their regulatory role on FOXM1 by mediating hypoxia-inducible factor 1α (HIF-1α) stabilization. Further research showed that NOX4-derived MitoROS-induced HIF-1α directly activates the transcription of FOXM1 and results in increased FOXM1 expression. Overexpression of NOX4 or FOXM1 promoted aerobic glycolysis, whereas knockdown of NOX4 or FOXM1 significantly suppressed aerobic glycolysis, in glioblastoma cells. NOX4-induced aerobic glycolysis was dependent on elevated FOXM1 expression, as FOXM1 knockdown abolished NOX4-induced aerobic glycolysis in glioblastoma cells both in vitro and in vivo. CONCLUSION: Increased expression of FOXM1 induced by NOX4-derived MitoROS plays a pivotal role in aerobic glycolysis, and our findings suggest that inhibition of NOX4-FOXM1 signaling may present a potential therapeutic target for glioblastoma treatment.
Assuntos
Neoplasias Encefálicas/metabolismo , Proteína Forkhead Box M1/metabolismo , Glioblastoma/metabolismo , NADPH Oxidase 4/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Efeito Warburg em Oncologia , Trifosfato de Adenosina/metabolismo , Animais , Western Blotting , Encéfalo/metabolismo , Neoplasias Encefálicas/terapia , Linhagem Celular Tumoral , Proteína Forkhead Box M1/antagonistas & inibidores , Glioblastoma/terapia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ácido Láctico/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/metabolismo , NADPH Oxidase 4/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Transplante de NeoplasiasRESUMO
Current studies on tumor progression focus on the roles of cytokines in the tumor microenvironment (TME), and recent research shows that transforming growth factor-ß1 (TGF-ß1) released from TME plays a pivotal role in tumor development and malignant transformation. The alteration in cellular metabolism is a hallmark of cancer, which not only provides cancer cells with ATP for fuel cellular reactions, but also generates metabolic intermediates for the synthesis of essential cellular ingredients, to support cell proliferation, migration, and invasion. Interestingly, we found a distinct metabolic change during TGF-ß1-induced epithelial-mesenchymal transition (EMT) in glioblastoma cells. Indeed, TGF-ß1 participates in metabolic reprogramming, and the molecular basis is still not well understood. NADPH oxidases 4 (NOX4), a member of the Nox family, also plays a key role in the biological effects of glioblastoma. However, the relationship between NOX4, TGF-ß1, and cellular metabolic changes during EMT in glioblastoma remains obscure. Here, our findings demonstrated that TGF-ß1 upregulated NOX4 expression accompanied by reactive oxygen species (ROS) through Smad-dependent signaling and then induced hypoxia-inducible factor 1α (HIF-1α) overexpression and nuclear accumulation resulting in metabolic reprogramming and promoting EMT. Besides, inhibition of glycolysis reversed EMT suggesting a causal relationship between TGF-ß1-induced metabolic changes and tumorigenesis. Moreover, TGF-ß1-induced metabolic reprogramming and EMT which modulated by NOX4/ROS were blocked when the phosphoinositide3-kinase (PI3K)/AKT/HIF-1α signaling pathways were inhibited. In conclusion, these suggest that NOX4/ROS induction by TGF-ß1 can be one of the main mechanisms mediating the metabolic reprogramming during EMT of glioblastoma cells and provide promising strategies for cancer therapy.
Assuntos
Glioblastoma/genética , NADPH Oxidase 4/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Transição Epitelial-Mesenquimal , Glioblastoma/patologia , Humanos , Masculino , Camundongos , Camundongos Nus , Transdução de Sinais , TransfecçãoRESUMO
OBJECTIVE: To develop an automated chimeric analysis and reporting platform based on short tandem repeat (STR) and capillary electrophoresis methods for allogeneic hematopoietic stem cell transplantation (allo-HSCT) so as to improve work efficiency. METHODS: Apache, MySQL, PHP and HTML5 were used to build the database and interface. The STR locus geno typing and chimeric analysis logic and flow were set up on the basis of STR rules and capillary electrophoresis. STR genotyping and 194 times of chimeric testing data of 100 patients after allo-HSCT were used to test the platform for automatic STR locus genotyping, chimeric calculation and report generation. RESULTS: The established platform could realize the functions of STR locus customization, STR genotype determination, automatic chimeric analysis, and detection information database management, which can automatically generate an integrated report including multiple sequential chimeric results and trend graphs for the same patient and can be accessed and used simultaneously by different users through different browser interfaces. The results of automated analysis by the platform are completely consistent with that of manual analysis by experienced technicians, and the possibility of manual analysis error is reduced through automation. The time required for automatic analysis using this platform is approximately 1/6-1/5 of manual analysis. CONCLUSION: The automatic analysis platform built in this study is operation stable and reliable in analysis results, which can improve work efficiency and report connotation, thus worthing popularized and applicable.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Eletroforese Capilar , Genótipo , Humanos , Repetições de Microssatélites , Doadores de TecidosRESUMO
Benzene is a toxic contaminant and can harm many aquatic species and cause serious damages to the river eco-system, if released to rivers. In 2012, a major spill accident occurred on the Huaihe River in Eastern China with 3 tons of benzene released to the river section 70 km upstream of a natural reserve. Two emergency measures were taken to minimize the impact of the accident on the natural reserve: 1) flow control by adjusting upstream sluices to delay the arrival of the contaminant plume at the reserve and 2) in-situ treatment using activated carbons to reduce the contaminant concentration. Here we develop a process-based mathematical model to analyze the monitoring data collected shortly after the accident, and explore not only how effective the adopted measures were over the incident but more importantly the mechanisms and critical conditions underlying the effectiveness of these measures. The model can be used as a tool for designing optimal management responses to similar spill accidents in regulated river systems, combining flow control and in-situ treatment.
Assuntos
Rios , Poluentes Químicos da Água , Benzeno , Carvão Vegetal , China , Monitoramento AmbientalRESUMO
OBJECTIVE: Glioma is one of the leading causes of death worldwide with high incidence, recurrence, and mortality. Interleukin-10 (IL-10) is a cytokine with dual function in many types of tumors. Although IL-10 is overexpressed and promotes tumor progression in human primary brain tumor, the mechanisms are largely unknown. MATERIALS AND METHODS: Glioma cells were treated with different dosages of IL-10. The cell growth was detected by CCK-8, and the invasion was measured by Transwell. The relative expression of messenger RNAs was detected by quantitative real-time polymerase chain reaction. RESULTS: We found that IL-10 treatment significantly enhanced glioma cell growth and invasion. Moreover, KPNA2 was significantly upregulated after treatment with IL-10. By performing knockdown experiments, we found that the glioma cell growth and invasion were significantly declined. CONCLUSIONS: The results indicated that knockdown of KPNA2 significantly inhibited the growth and invasion of glioma cells. Moreover, IL-10 promotes glioma progression via upregulation of KPNA2. This study will be of important significance and provides a potential target for treatment of patients with glioma.
Assuntos
Neoplasias Encefálicas/patologia , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Interleucina-10/metabolismo , alfa Carioferinas/metabolismo , Apoptose , Neoplasias Encefálicas/genética , Glioma/genética , Humanos , Técnicas In Vitro , Interleucina-10/antagonistas & inibidores , Interleucina-10/genética , Invasividade Neoplásica , RNA Interferente Pequeno/genética , Células Tumorais Cultivadas , alfa Carioferinas/genéticaRESUMO
PURPOSE: Chemotherapy after surgery can prolong the survival of patients with gliomas. Dimethylaminomicheliolide (DMAMCL), a novel chemotherapeutic agent, exhibited antitumor properties in acute myeloid leukemia stem cells and showed an increased drug concentration in the brain. This study aims to investigate the specific anticancer activities and mechanisms of DMAMCL in glioma cells. MATERIALS AND METHODS: In this study, the effects of DMAMCL were evaluated and characterized in U87-MG and U251 glioma cells. Cell viability was assessed by Cell Counting Kit-8. Apoptosis, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) generation were assessed by fluorescence microscopy. Autophagosome formation was observed with transmission electron microscopy, and the autophagy flux was measured by transfecting cells with mRFP-GFP-LC3 adenoviral vectors. Immunofluorescence and Western blot analyses were used to determine the expression of proteins. RESULTS: In the present study, treatment with DMAMCL decreased cell viability and induced apoptosis in U87-MG and U251 glioma cells. Additionally, DMAMCL activated autophagy-mediated cell death as evidenced by the formation of autophagosomes, accumulation of LC3B-II, inhibition of autophagy flux, and increase in cell viability after cotreatment with an autophagy inhibitor. Subsequent experiments showed that the DMAMCL-induced apoptosis and autophagy were possibly mediated by ROS generation and Akt/mTOR signaling pathway inhibition. On the other hand, the ROS scavenger N-acetyl-L-cysteine and the Akt activator insulin-like growth factor-1 attenuated the DMAMCL-induced autophagy and cell death. CONCLUSION: Our findings revealed that DMAMCL induced apoptosis and autophagic cell death by regulating the ROS/mitogen-activated protein kinase signaling pathway and suppressing the Akt/mTOR signaling pathway in human glioma cells. DMAMCL may be a novel effective anticancer agent, which can target gliomas.
RESUMO
BACKGROUND: Cancer cells maintain energy metabolism mainly by glycolysis, even under sufficient oxygen conditions. It gives cancer cells better growth advantages under complicated internal environment. KPNA2 is a novel oncogene that has received much attention in recent years, but the exact mechanisms of KPNA2 in tumorigenesis and progression are largely unknown. Especially its potential roles in the metabolic transformation of tumors still remain to be explored. METHODS: The expressions of KPNA2 in glioblastoma and normal human brain samples were analyzed by immunohistochemical analysis. The activities of key enzymes in glycolysis, the production of lactate acid and glucose uptake were investigated by colorimetry. GLUT-1 expression was measured by flow cytometry. CCK8 was used to examine the cell viability in vitro, and the xenograft models in nude mice were established to explore the roles of KPNA2 in vivo. In addition, Co-IP, subcellular fractionation, western blot, immunofluorescence and luciferase assay were used to investigate the internal connection between KPNA2, c-myc and E2F1. RESULTS: In the present study, we found that KPNA2 was highly expressed in the glioma compared to the normal brain tissues. Level of KPNA2 was an independent predictor of prognosis in the glioma patients. Knockdown of KPNA2 in the glioblastoma cell lines U87 and U251 decreased deoxyglucose uptake, activities of the key glycolytic enzymes and lactate production. The level of oxidative phosphorylation (OXPHOS) was moderately decreased. Additioanlly, tumor proliferation and invasiveness were concomitantly downregulated. We have identified c-myc as a potential mediator of KPNA2. Aberrant expression of KPNA2 significantly changed the subcellular distribution of c-myc as well as its expression level. E2F1, another key cargo protein of KPNA2, was further identified to play a potential role in regulating the transcription of c-myc by KPNA2. CONCLUSIONS: Our findings suggested that KPNA2, a potential tumor oncogene, performs its function in part via regulating cellular metabolism through c-myc signaling axis. It would provide a possible explanation for Warburg effect and thus offer a new perspective to the roles of KPNA2 in gliomagenesis.
Assuntos
Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , alfa Carioferinas/metabolismo , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Glioblastoma/genética , Glioblastoma/patologia , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Fosforilação Oxidativa , Proteínas Proto-Oncogênicas c-myc/genética , Transdução de Sinais , Transfecção , alfa Carioferinas/biossíntese , alfa Carioferinas/genéticaRESUMO
S100B, a member of the multigene family of Ca2+-binding proteins, is overexpressed by most malignant gliomas but its biological role in gliomagenesis is unclear. Recently, we demonstrated that low concentrations of S100B attenuated microglia activation through the induction of STAT3. Furthermore, S100B downregulation in a murine glioma model inhibited macrophage trafficking and tumor growth. Based on these observations, we hypothesized that S100B inhibitors may have antiglioma properties through modulation of tumor microenvironment. To discover novel S100B inhibitors, we developed a high-throughput screening cell-based S100B promoter-driven luciferase reporter assay. Initial screening of 768 compounds in the NIH library identified 36 hits with >85% S100B inhibitory activity. Duloxetine (Dul, an SNRI) was selected for the initial proof-of-concept studies. At low concentrations (1-5⯵M) Dul inhibited S100B and CCL2 production in mouse GL261 glioma cells, but had minimal cytotoxic activity in vitro. In vivo, however, Dul (30â¯mg/kg/14 days) inhibited S100B production, altered the polarization and trafficking of tumor-associated myeloid-derived cells, and inhibited the growth of intracranial GL261 gliomas. Dul therapeutic efficacy, however, was not observed in the K-Luc glioma model that expresses low levels of S100B. These findings affirm the role of S100B in gliomagenesis and justify the development of more potent S100B inhibitors for glioma therapy.
Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Cloridrato de Duloxetina/farmacologia , Glioma/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Células Mieloides/efeitos dos fármacos , Subunidade beta da Proteína Ligante de Cálcio S100/antagonistas & inibidores , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Glioma/genética , Glioma/metabolismo , Humanos , Estimativa de Kaplan-Meier , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Células Mieloides/metabolismo , Células Mieloides/patologia , Subunidade beta da Proteína Ligante de Cálcio S100/genética , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Inibidores da Recaptação de Serotonina e Norepinefrina/farmacologia , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Intracranial primary collision tumors of different histologic types are rare, and their occurrence is still unclear. CASE DESCRIPTION: We describe a 66-year-old female who presented with headache, nausea, and vomiting. Magnetic resonance imaging scan showed that there were 2 primary intracranial tumors occurring simultaneously at adjacent sites of the right cerebral hemisphere. Tumor pathology showed 2 distinct tumors: meningioma (World Health Organization I) and glioblastoma. This is a rare case in which 2 different intracranial primary tumors occurred at adjacent sites, but the patient had no history of head trauma, neurologic surgery, or radiation therapy. CONCLUSIONS: According to previous and present reports, the most common type of intracranial primary collision tumor is composed of a benign meningioma and a glioblastoma. During the occurrence of collision tumors, 1 tumor can play a role in the formation and growth of the other.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Meníngeas , Meningioma , Neoplasias Primárias Múltiplas , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Glioblastoma/cirurgia , Humanos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/patologia , Meningioma/cirurgia , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgiaRESUMO
Enhancer of zeste homolog 2 (EZH2) is a critical component of the polycomb repressive complex 2, which epigenetically represses genes involved in tumorigenesis and is highly expressed in tumors. However, no studies have investigated EZH2 expression and its clinical significance in human pituitary adenomas (PAs). Therefore, we examined the expression pattern of EZH2 in PAs and studied the correlations between protein expression and invasiveness, proliferation, angiogenesis, hormone functioning, and some other factors. We measured EZH2 and MMP-14 protein and EZH2 mRNA expression in 62 samples of PAs by immunohistochemistry staining and quantitative real-time polymerase chain reaction and correlated protein expression relative to clinicopathologic features. The immunopositive rate of EZH2 was 88.7% (55/62). The extent of expression was associated with invasiveness, microvessel density, and proliferation (Ki-67 index). Moreover, EZH2 expression correlated with MMP-14 expression. We did not find any correlation between EZH2 overexpression and hormone-secreting function or patient age or sex. The quantitative real-time polymerase chain reaction analysis revealed that the amount of EZH2 mRNA was significantly higher in invasive than in noninvasive adenomas. This is the first report to describe EZH2 overexpression in human PAs, especially invasive adenomas. Thus, EZH2 is a potentially useful diagnostic marker and pharmacotherapeutic target for invasive PAs.
Assuntos
Adenoma/química , Biomarcadores Tumorais/análise , Movimento Celular , Proliferação de Células , Proteína Potenciadora do Homólogo 2 de Zeste/análise , Neovascularização Patológica , Neoplasias Hipofisárias/química , Adenoma/genética , Adenoma/patologia , Biomarcadores Tumorais/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Masculino , Metaloproteinase 14 da Matriz/análise , Metaloproteinase 14 da Matriz/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Transcrição Gênica , Regulação para CimaRESUMO
BACKGROUND Pituitary adenomas are mostly benign tumors, although certain cases have invasiveness, which might be related with high expression of miR-106b. The PTEN-PI3K/AKT signal pathway is known to be related with cell migration and invasion. Among these, PTEN is the target gene for miR-106b. Whether miR-106b affects invasiveness of pituitary adenoma via PTEN-PI3K/AKT is unclear. MATERIAL AND METHODS Both invasive and non-invasive pituitary adenoma tissue samples were collected from our Neurosurgery Department, in parallel with brain tissues after head contusion surgery. Pituitary adenoma cell line HP75 was cultured in vitro and divided into NC and miR-106b inhibitor groups for measuring cell cycle/proliferation. Malignant growth of cells was measured by agarose gel clonal assay, while cell migration and invasion were reflected by starch assay and Transwell assay, respectively. The expression of PTEN, PI3K/AKT, and MMP-9 was measured. RESULTS MiR-106b was significantly up-regulated in pituitary adenoma but PTEN was down-regulated, especially in invasive tumors. The inhibition of miR-106b remarkably suppressed proliferation and anchorage-independent growth of HP75 cells, with major arrest of cell cycles. The inhibition of miR-106b significantly depressed starch healing and invasive potency of cells. A negative targeted regulation existed between miR-106b and PTEN, as the inhibition of miR-106b significantly enhanced PTEN expression, affecting the activity of downstream PI3K/AKT signaling pathway, thus affecting migration and invasion of pituitary adenoma. CONCLUSIONS MiR-106b can affect migration and invasion of pituitary adenoma cells via regulating PTEN and further activity of the PI3K/AKT signaling pathway and MMP-9 expression.